Functional and Potential Therapeutic Implication of MicroRNAs in Pancreatic Cancer
Abstract
:1. Introduction
2. miRNAs in Pancreatic Cancer
2.1. miRNAs with Tumor-Inhibitory Functions
2.2. miRNAs with Oncogenic Functions
2.3. MicroRNAs in Chemoresistance
2.4. miRNAs in Pancreatic Cancer Stem Cells
2.5. miRNAs in Tumor Microenvironment and Immune Infiltration
miRNA | Dysregulation | Targets | References |
miR-15a | Downregulated | WEE1, CHK1, BMI-1, BCL2, Yap-1, and DCLK1, WNT3a, FGF7 Cellular pathways, proliferation, EMT | [35,37,38,102] |
miR-142 | Downregulated | FAK, MMP9, PIK3CA, HIF-1α Migration, angiogenesis, invasion | [40,41] |
miR-145 | Downregulated | TGF-β receptor, angiopoietin-2 and SMAD2, MUC13, KRAS, RREB1 Proliferation, migration, invasion, RAS signaling, angiogenesis | [42,43,103] |
miR-373 | Downregulated | CCND2 Propagation, migration, invasion, chemosensitivity to gemcitabine | [104,105] |
miR-Let-7 | Downregulated | KRAS, STAT3, IGF2BP, and HMGA1/HMGA2, SOX13 Progression and invasion | [106,107] |
miR-141 | Downregulated | MAP4K4 Proliferation and invasion | [108] |
miR-34 | Downregulated | Snail1, Notch1 Progression and invasion | [103,109] |
miR-506 | Downregulated | STAT3, PIM3 Polarization of M2-like macrophages, promotes antitumor immune response, overcomes immunotherapy resistance | [108] |
miR-409 | Downregulated | GAB1 Cell cycle progression, migration, invasion | [110] |
miR-96 | Downregulated | NUAK1, KRAS Antiproliferative, Proapoptotic and Antimetastatic properties | [111,112] |
miR-217 | Downregulated | Tpd52l2, ATAD2 PIK3CA/AKT signaling pathways, inactivation of the AKT signaling pathway | [113,114] |
miR-873 | Downregulated | PLEK2, KRAS PI3K/AKT pathway | [115,116] |
miR-33a | Downregulated | AMPK, METTL3, RAP2A MTOR signaling, EMT, metabolic reprogramming | [117,118,119] |
miR-198 | Downregulated | MSLN, OCT-2, PBX-1, VCP Growth and metastases | [120] |
miR-433 | Downregulated | GOT1 Proliferation, metabolic reprogramming | [121] |
miR-21 | Upregulated | PDCD4, Timp3, PTEN, RECK, Spry2 MAPK/ERK and PI3K/AKT signaling pathways. | [75,122,123,124] |
miR-221 | Upregulated | RB1, TIMP-2, KIT, CDKN1B, RUNX2 and BCL2 5-fluorouracil resistance, cell proliferation | [62,125,126] |
miR-155 | Upregulated | TP53INP1 Apoptosis | [127] |
miR-27 | Upregulated | BTG2 Wnt/β-catenin pathway | [128,129] |
miR-196a | Upregulated | NFKBIA Proliferation, migration | [130] |
miR-194 | Upregulated | PD-L1, DACH1 Anti-tumor immunity, progression | [131,132] |
miR-212 | Upregulated | patched-1, Rb1 Hedgehog signalling, cell cycle progression | [59,133] |
miR-29a | Upregulated | TTP EMT, Wnt/B-catenin | [134] |
miR-191 | Upregulated | HIF-1, USP10 Cell cycle progression | [135,136] |
miR-23a | Upregulated | FOXP2, TGFBR2, TFPI-2 Proliferation and invasion | [71,137,138] |
3. Potential Use of miRNA-Based Therapeutics for Pancreatic Cancer: Key Features and Limitations
3.1. Restoration of Tumor-Suppressive miRNAs
3.2. Suppressing miRNAs with Oncogenic Function
3.3. Combination Therapy
3.4. Modification of miRNAs to Treat Pancreatic Cancer
3.5. Limitations of miRNA-Based Therapeutics
4. Conclusions
Funding
Acknowledgments
Conflicts of Interest
References
- Siegel, R.L.; Miller, K.D.; Fuchs, H.E.; Jemal, A. Cancer statistics, 2022. CA Cancer J. Clin. 2022, 72, 7–33. [Google Scholar] [CrossRef] [PubMed]
- Taherian, M.; Wang, H.; Wang, H. Pancreatic Ductal Adenocarcinoma: Molecular Pathology and Predictive Biomarkers. Cells 2022, 11, 3068. [Google Scholar] [CrossRef] [PubMed]
- Deshwar, A.B.; Sugar, E.; Torto, D.; Ana De Jesus-Acosta, A.D.J.-A.; Weiss, M.J.; Wolfgang, C.L.; Le, D.; He, J.; Burkhart, R.; Zheng, L.; et al. Diagnostic intervals and pancreatic ductal adenocarcinoma (PDAC) resectability: A single-center retrospective analysis. Ann. Pancreat. Cancer 2018, 1, 13. [Google Scholar] [CrossRef] [PubMed]
- Grant, T.J.; Hua, K.; Singh, A. Molecular Pathogenesis of Pancreatic Cancer; Elsevier: Amsterdam, The Netherlands, 2016; pp. 241–275. [Google Scholar]
- Gutiérrez, M.L.; Muñoz-Bellvís, L.; Orfao, A. Genomic Heterogeneity of Pancreatic Ductal Adenocarcinoma and Its Clinical Impact. Cancers 2021, 13, 4451. [Google Scholar] [CrossRef] [PubMed]
- American Cancer Society. Facts & Figures 2023; American Cancer Society: Atlanta, GA, USA, 2023. [Google Scholar]
- Lee, H.S.; Park, S.W. Systemic Chemotherapy in Advanced Pancreatic Cancer. Gut Liver 2016, 10, 340–347. [Google Scholar] [CrossRef]
- Von Hoff, D.D.; Ervin, T.; Arena, F.P.; Chiorean, E.G.; Infante, J.; Moore, M.; Seay, T.; Tjulandin, S.A.; Ma, W.W.; Saleh, M.N.; et al. Increased Survival in Pancreatic Cancer with nab-Paclitaxel plus Gemcitabine. N. Engl. J. Med. 2013, 369, 1691–1703. [Google Scholar] [CrossRef] [PubMed]
- Gupta, S.; El-Rayes, B.F. Small molecule tyrosine kinase inhibitors in pancreatic cancer. Biol. Targets Ther. 2008, 2, 707–715. [Google Scholar] [CrossRef]
- Zeng, S.; Pöttler, M.; Lan, B.; Grützmann, R.; Pilarsky, C.; Yang, H. Chemoresistance in Pancreatic Cancer. Int. J. Mol. Sci. 2019, 20, 4504. [Google Scholar] [CrossRef]
- Chu, X.; Wei, D.; Liu, X.; Long, D.; Tian, X.; Yang, Y. MicroRNAs as potential therapeutic targets for pancreatic cancer. Chin. Med. J. 2022, 135, 4–10. [Google Scholar] [CrossRef]
- Fesler, A.; Ju, J. Development of microRNA-based therapy for pancreatic cancer. J. Pancreatol. 2019, 2, 147–151. [Google Scholar] [CrossRef]
- Yuen, J.G.; Hwang, G.-R.; Fesler, A.; Intriago, E.; Pal, A.; Ojha, A.; Ju, J. Development of Gemcitabine-Modified miRNA Mimics as Cancer Therapeutics for Pancreatic Ductal Adenocarcinoma. bioRxiv 2023. [CrossRef]
- Vahabi, M.; Dehni, B.; Antomás, I.; Giovannetti, E.; Peters, G.J. Targeting miRNA and using miRNA as potential therapeutic options to bypass resistance in pancreatic ductal adenocarcinoma. Cancer Metastasis Rev. 2023, 42, 725–740. [Google Scholar] [CrossRef] [PubMed]
- Wang, J.; Chen, J.; Sen, S. MicroRNA as Biomarkers and Diagnostics. J. Cell. Physiol. 2016, 231, 25–30. [Google Scholar] [CrossRef] [PubMed]
- Xi, Y.; Nakajima, G.; Gavin, E.; Morris, C.G.; Kudo, K.; Hayashi, K.; Ju, J. Systematic analysis of microRNA expression of RNA extracted from fresh frozen and formalin-fixed paraffin-embedded samples. RNA 2007, 13, 1668–1674. [Google Scholar] [CrossRef] [PubMed]
- Huang, J.; Liu, J.; Chen-Xiao, K.; Zhang, X.; Lee, W.N.P.; Go, V.L.W.; Xiao, G.G. Advance in microRNA as a potential biomarker for early detection of pancreatic cancer. Biomark. Res. 2016, 4, 20. [Google Scholar] [CrossRef] [PubMed]
- Ali Syeda, Z.; Langden, S.S.S.; Munkhzul, C.; Lee, M.; Song, S.J. Regulatory Mechanism of MicroRNA Expression in Cancer. Int. J. Mol. Sci. 2020, 21, 1723. [Google Scholar] [CrossRef]
- Huang, X.; Zhu, X.; Yu, Y.; Zhu, W.; Jin, L.; Zhang, X.; Li, S.; Zou, P.; Xie, C.; Cui, R. Dissecting miRNA signature in colorectal cancer progression and metastasis. Cancer Lett. 2021, 501, 66–82. [Google Scholar] [CrossRef]
- Rupaimoole, R.; Slack, F.J. MicroRNA therapeutics: Towards a new era for the management of cancer and other diseases. Nat. Rev. Drug Discov. 2017, 16, 203–222. [Google Scholar] [CrossRef]
- Palanichamy, J.K.; Rao, D.S. miRNA dysregulation in cancer: Towards a mechanistic understanding. Front. Genet. 2014, 5, 54. [Google Scholar] [CrossRef]
- Fathi, M.; Ghafouri-Fard, S.; Abak, A.; Taheri, M. Emerging roles of miRNAs in the development of pancreatic cancer. Biomed. Pharmacother. Biomed. Pharmacother. 2021, 141, 111914. [Google Scholar] [CrossRef]
- Raphael, B.J.; Hruban, R.H.; Aguirre, A.J.; Moffitt, R.A.; Yeh, J.J.; Stewart, C.; Robertson, A.G.; Cherniack, A.D.; Gupta, M.; Getz, G.; et al. Integrated Genomic Characterization of Pancreatic Ductal Adenocarcinoma. Cancer Cell 2017, 32, 185–203.e113. [Google Scholar] [CrossRef]
- Lee, E.J.; Gusev, Y.; Jiang, J.; Nuovo, G.J.; Lerner, M.R.; Frankel, W.L.; Morgan, D.L.; Postier, R.G.; Brackett, D.J.; Schmittgen, T.D. Expression profiling identifies microRNA signature in pancreatic cancer. Int. J. Cancer 2007, 120, 1046–1054. [Google Scholar] [CrossRef]
- Menon, A.; Abd-Aziz, N.; Khalid, K.; Poh, C.L.; Naidu, R. miRNA: A Promising Therapeutic Target in Cancer. Int. J. Mol. Sci. 2022, 23, 11502. [Google Scholar] [CrossRef]
- Bravo-Vázquez, L.A.; Frías-Reid, N.; Ramos-Delgado, A.G.; Osorio-Pérez, S.M.; Zlotnik-Chávez, H.R.; Pathak, S.; Banerjee, A.; Bandyopadhyay, A.; Duttaroy, A.K.; Paul, S. MicroRNAs and long non-coding RNAs in pancreatic cancer: From epigenetics to potential clinical applications. Transl. Oncol. 2023, 27, 101579. [Google Scholar] [CrossRef]
- Bartel, D.P. MicroRNAs. Cell 2004, 116, 281–297. [Google Scholar] [CrossRef] [PubMed]
- Zhang, X.; Sai, B.; Wang, F.; Wang, L.; Wang, Y.; Zheng, L.; Li, G.; Tang, J.; Xiang, J. Hypoxic BMSC-derived exosomal miRNAs promote metastasis of lung cancer cells via STAT3-induced EMT. Mol. Cancer 2019, 18, 40. [Google Scholar] [CrossRef] [PubMed]
- Pan, G.; Liu, Y.; Shang, L.; Zhou, F.; Yang, S. EMT-associated microRNAs and their roles in cancer stemness and drug resistance. Cancer Commun. 2021, 41, 199–217. [Google Scholar] [CrossRef] [PubMed]
- Garzon, R.; Fabbri, M.; Cimmino, A.; Calin, G.A.; Croce, C.M. MicroRNA expression and function in cancer. Trends Mol. Med. 2006, 12, 580–587. [Google Scholar] [CrossRef] [PubMed]
- Hong, T.H.; Park, I.Y. MicroRNA expression profiling of diagnostic needle aspirates from surgical pancreatic cancer specimens. Ann. Surg. Treat. Res. 2014, 87, 290. [Google Scholar] [CrossRef] [PubMed]
- Rashid, S.; Rashid, S.; Das, P.; Singh, N.; Dash, N.R.; Nayak, B.; Sati, H.C.; Chauhan, S.S.; Gupta, S.; Saraya, A. Clinical significance of Notch pathway-associated microRNA-107 in pancreatic ductal adenocarcinoma. Future Oncol. 2023, 19, 1003–1012. [Google Scholar] [CrossRef] [PubMed]
- Distefano, R.; Tomasello, L.; Rampioni Vinciguerra, G.L.; Gasparini, P.; Xiang, Y.; Bagnoli, M.; Marceca, G.P.; Fadda, P.; Laganà, A.; Acunzo, M.; et al. Pan-Cancer Analysis of Canonical and Modified miRNAs Enhances the Resolution of the Functional miRNAome in Cancer. Cancer Res. 2022, 82, 3687–3700. [Google Scholar] [CrossRef] [PubMed]
- Otmani, K.; Lewalle, P. Tumor Suppressor miRNA in Cancer Cells and the Tumor Microenvironment: Mechanism of Deregulation and Clinical Implications. Front. Oncol. 2021, 11, 708765. [Google Scholar] [CrossRef] [PubMed]
- Zhang, X.J.; Ye, H.; Zeng, C.W.; He, B.; Zhang, H.; Chen, Y.Q. Dysregulation of miR-15a and miR-214 in human pancreatic cancer. J. Hematol. Oncol. 2010, 3, 46. [Google Scholar] [CrossRef] [PubMed]
- Pekarsky, Y.; Croce, C.M. Role of miR-15/16 in CLL. Cell Death Differ. 2015, 22, 6–11. [Google Scholar] [CrossRef]
- Guo, S.; Xu, X.; Tang, Y.; Zhang, C.; Li, J.; Ouyang, Y.; Ju, J.; Bie, P.; Wang, H. miR-15a inhibits cell proliferation and epithelial to mesenchymal transition in pancreatic ductal adenocarcinoma by down-regulating Bmi-1 expression. Cancer Lett. 2014, 344, 40–46. [Google Scholar] [CrossRef] [PubMed]
- Guo, S.; Fesler, A.; Huang, W.; Wang, Y.; Yang, J.; Wang, X.; Zheng, Y.; Hwang, G.-R.; Wang, H.; Ju, J. Functional Significance and Therapeutic Potential of miR-15a Mimic in Pancreatic Ductal Adenocarcinoma. Mol. Ther. Nucleic Acids 2020, 19, 228–239. [Google Scholar] [CrossRef] [PubMed]
- Yao, R.; Xu, L.; Wei, B.; Qian, Z.; Wang, J.; Hui, H.; Sun, Y. miR-142-5p regulates pancreatic cancer cell proliferation and apoptosis by regulation of RAP1A. Pathol. Res. Pract. 2019, 215, 152416. [Google Scholar] [CrossRef]
- Lu, Y.; Ji, N.; Wei, W.; Sun, W.; Gong, X.; Wang, X. MiR-142 modulates human pancreatic cancer proliferation and invasion by targeting hypoxia-inducible factor 1 (HIF-1α) in the tumor microenvironments. Biol. Open 2017, 6, 252–259. [Google Scholar] [CrossRef]
- Zhu, J.; Zhou, L.; Wei, B.; Qian, Z.; Wang, J.; Hui, H.; Sun, Y. miR-142-5p inhibits pancreatic cancer cell migration and invasion by targeting PIK3CA. Mol. Med. Rep. 2020, 22, 2085–2092. [Google Scholar] [CrossRef]
- Khan, S.; Ebeling, M.C.; Zaman, M.S.; Sikander, M.; Yallapu, M.M.; Chauhan, N.; Yacoubian, A.M.; Behrman, S.W.; Zafar, N.; Kumar, D.; et al. MicroRNA-145 targets MUC13 and suppresses growth and invasion of pancreatic cancer. Oncotarget 2014, 5, 7599–7609. [Google Scholar] [CrossRef]
- Chen, S.; Xu, J.; Su, Y.; Hua, L.; Feng, C.; Lin, Z.; Huang, H.; Li, Y. MicroRNA-145 suppresses epithelial to mesenchymal transition in pancreatic cancer cells by inhibiting TGF-β signaling pathway. J. Cancer 2020, 11, 2716–2723. [Google Scholar] [CrossRef]
- Han, T.; Yi, X.-P.; Liu, B.; Ke, M.-J.; Li, Y.-X. MicroRNA-145 suppresses cell proliferation, invasion and migration in pancreatic cancer cells by targeting NEDD9. Mol. Med. Rep. 2015, 11, 4115–4120. [Google Scholar] [CrossRef] [PubMed]
- Wang, H.; Hang, C.; Ou, X.-L.; Nie, J.-S.; Ding, Y.-T.; Xue, S.-G.; Gao, H.; Zhu, J.-X. MiR-145 functions as a tumor suppressor via regulating angiopoietin-2 in pancreatic cancer cells. Cancer Cell Int. 2016, 16, 65. [Google Scholar] [CrossRef] [PubMed]
- Liu, M.; Zhang, Y.; Yang, J.; Zhan, H.; Zhou, Z.; Jiang, Y.; Shi, X.; Fan, X.; Zhang, J.; Luo, W.; et al. Zinc-Dependent Regulation of ZEB1 and YAP1 Coactivation Promotes Epithelial-Mesenchymal Transition Plasticity and Metastasis in Pancreatic Cancer. Gastroenterology 2021, 160, 1771–1783. [Google Scholar] [CrossRef] [PubMed]
- Lehmann, W.; Mossmann, D.; Kleemann, J.; Mock, K.; Meisinger, C.; Brummer, T.; Herr, R.; Brabletz, S.; Stemmler, M.P.; Brabletz, T. ZEB1 turns into a transcriptional activator by interacting with YAP1 in aggressive cancer types. Nat. Commun. 2016, 7, 10498. [Google Scholar] [CrossRef] [PubMed]
- Mori, M.; Triboulet, R.; Mohseni, M.; Schlegelmilch, K.; Shrestha, K.; Camargo, F.D.; Gregory, R.I. Hippo Signaling Regulates Microprocessor and Links Cell-Density-Dependent miRNA Biogenesis to Cancer. Cell 2014, 156, 893–906. [Google Scholar] [CrossRef] [PubMed]
- Zhang, Y.; Yang, J.; Cui, X.; Chen, Y.; Zhu, V.F.; Hagan, J.P.; Wang, H.; Yu, X.; Hodges, S.E.; Fang, J.; et al. A novel epigenetic CREB-miR-373 axis mediates ZIP4-induced pancreatic cancer growth. EMBO Mol. Med. 2013, 5, 1322–1334. [Google Scholar] [CrossRef] [PubMed]
- Lin, X.; Zheng, L.; Song, H.; Xiao, J.; Pan, B.; Chen, H.; Jin, X.; Yu, H. Effects of microRNA-183 on epithelial-mesenchymal transition, proliferation, migration, invasion and apoptosis in human pancreatic cancer SW1900 cells by targeting MTA1. Exp. Mol. Pathol. 2017, 102, 522–532. [Google Scholar] [CrossRef]
- Patel, K.; Kollory, A.; Takashima, A.; Sarkar, S.; Faller, D.V.; Ghosh, S.K. MicroRNA let-7 downregulates STAT3 phosphorylation in pancreatic cancer cells by increasing SOCS3 expression. Cancer Lett. 2014, 347, 54–64. [Google Scholar] [CrossRef]
- Shao, Z.; Chen, X.; Qiu, H.; Xu, M.; Wen, X.; Chen, Z.; Liu, Z.; Ding, X.; Zhang, L. CircNEK6 promotes the progression of pancreatic ductal adenocarcinoma through targeting miR-503/CCND1 axis. Transl. Oncol. 2024, 39, 101810. [Google Scholar] [CrossRef]
- Xu, B.; Gong, X.; Zi, L.; Li, G.; Dong, S.; Chen, X.; Li, Y. Silencing of DLEU2 suppresses pancreatic cancer cell proliferation and invasion by upregulating microRNA-455. Cancer Sci. 2019, 110, 1676–1685. [Google Scholar] [CrossRef] [PubMed]
- Wu, X.; Chen, W.; Cai, H.; Hu, J.; Wu, B.; Jiang, Y.; Chen, X.; Sun, D.; An, Y. MiR-216b inhibits pancreatic cancer cell progression and promotes apoptosis by down-regulating KRAS. Arch. Med. Sci. 2018, 14, 1321–1332. [Google Scholar] [CrossRef] [PubMed]
- Jia, L.; Zhang, Y.; Pu, F.; Yang, C.; Yang, S.; Yu, J.; Xu, Z.; Yang, H.; Zhou, Y.; Zhu, S. Pseudogene AK4P1 promotes pancreatic ductal adenocarcinoma progression through relieving miR-375-mediated YAP1 degradation. Aging 2022, 14, 1983–2003. [Google Scholar] [CrossRef] [PubMed]
- Xu, W.; Lou, W.; Mei, L. A key regulatory loop AK4P1/miR-375/SP1 in pancreatic adenocarcinoma. Epigenetics 2023, 18, 2148433. [Google Scholar] [CrossRef]
- Su, Q.L.; Zhao, H.J.; Song, C.F.; Zhao, S.; Tian, Z.S.; Zhou, J.J. MicroRNA-383 suppresses pancreatic carcinoma development via inhibition of GAB1 expression. Eur. Rev. Med. Pharmacol. Sci. 2019, 23, 10729–10739. [Google Scholar] [CrossRef] [PubMed]
- Cheng, C.J.; Slack, F.J. The Duality of OncomiR Addiction in the Maintenance and Treatment of Cancer. Cancer J. 2012, 18, 232–237. [Google Scholar] [CrossRef]
- Ma, C.; Nong, K.; Wu, B.; Dong, B.; Bai, Y.; Zhu, H.; Wang, W.; Huang, X.; Yuan, Z.; Ai, K. miR-212 promotes pancreatic cancer cell growth and invasion by targeting the hedgehog signaling pathway receptor patched-1. J. Exp. Clin. Cancer Res. 2014, 33, 54. [Google Scholar] [CrossRef]
- Wang, H.-L.; Zhou, R.; Liu, J.; Chang, Y.; Liu, S.; Wang, X.-B.; Huang, M.-F.; Zhao, Q. MicroRNA-196b inhibits late apoptosis of pancreatic cancer cells by targeting CADM1. Sci. Rep. 2017, 7, 11467. [Google Scholar] [CrossRef]
- Liu, M.; Du, Y.; Gao, J.; Liu, J.; Kong, X.; Gong, Y.; Li, Z.; Wu, H.; Chen, H. Aberrant expression miR-196a is associated with abnormal apoptosis, invasion, and proliferation of pancreatic cancer cells. Pancreas 2013, 42, 1169–1181. [Google Scholar] [CrossRef]
- Li, F.; Xu, J.-W.; Wang, L.; Liu, H.; Yan, Y.; Hu, S.-Y. MicroRNA-221-3p is up-regulated and serves as a potential biomarker in pancreatic cancer. Artif. Cells Nanomed. Biotechnol. 2018, 46, 482–487. [Google Scholar] [CrossRef]
- Yang, W.; Yang, Y.; Xia, L.; Yang, Y.; Wang, F.; Song, M.; Chen, X.; Liu, J.; Song, Y.; Zhao, Y.; et al. MiR-221 Promotes Capan-2 Pancreatic Ductal Adenocarcinoma Cells Proliferation by Targeting PTEN-Akt. Cell. Physiol. Biochem. 2016, 38, 2366–2374. [Google Scholar] [CrossRef] [PubMed]
- Preis, M.; Gardner, T.B.; Gordon, S.R.; Pipas, J.M.; Mackenzie, T.A.; Klein, E.E.; Longnecker, D.S.; Gutmann, E.J.; Sempere, L.F.; Korc, M. MicroRNA-10b Expression Correlates with Response to Neoadjuvant Therapy and Survival in Pancreatic Ductal Adenocarcinoma. Clin. Cancer Res. 2011, 17, 5812–5821. [Google Scholar] [CrossRef]
- Huang, C.; Li, H.; Wu, W.; Jiang, T.; Qiu, Z. Regulation of miR-155 affects pancreatic cancer cell invasiveness and migration by modulating the STAT3 signaling pathway through SOCS1. Oncol. Rep. 2013, 30, 1223–1230. [Google Scholar] [CrossRef]
- Wang, P.; Zhu, C.-F.; Ma, M.-Z.; Chen, G.; Song, M.; Zeng, Z.-L.; Lu, W.-H.; Yang, J.; Wen, S.; Chiao, P.J.; et al. Micro-RNA-155 is induced by K-Ras oncogenic signal and promotes ROS stress in pancreatic cancer. Oncotarget 2015, 6, 21148–21158. [Google Scholar] [CrossRef]
- Xia, X.; Zhang, K.; Cen, G.; Jiang, T.; Cao, J.; Huang, K.; Huang, C.; Zhao, Q.; Qiu, Z. MicroRNA-301a-3p promotes pancreatic cancer progression via negative regulation of SMAD4. Oncotarget 2015, 6, 21046–21063. [Google Scholar] [CrossRef]
- Wang, X.; Luo, G.; Zhang, K.; Cao, J.; Huang, C.; Jiang, T.; Liu, B.; Su, L.; Qiu, Z. Hypoxic Tumor-Derived Exosomal miR-301a Mediates M2 Macrophage Polarization via PTEN/PI3Kγ to Promote Pancreatic Cancer Metastasis. Cancer Res. 2018, 78, 4586–4598. [Google Scholar] [CrossRef]
- Sun, J.; Jiang, Z.; Li, Y.; Wang, K.; Chen, X.; Liu, G. Downregulation of miR-21 inhibits the malignant phenotype of pancreatic cancer cells by targeting VHL. OncoTargets Ther. 2019, 12, 7215–7226. [Google Scholar] [CrossRef]
- Hao, J.; Zhang, S.; Zhou, Y.; Hu, X.; Shao, C. MicroRNA 483-3p suppresses the expression of DPC4/Smad4 in pancreatic cancer. FEBS Lett. 2011, 585, 207–213. [Google Scholar] [CrossRef]
- Wang, W.; Ning, J.Z.; Tang, Z.G.; He, Y.; Yao, L.-C.; Ye, L.; Wu, L. MicroRNA-23a acts as an oncogene in pancreatic carcinoma by targeting TFPI-2. Exp. Ther. Med. 2020, 20, 53. [Google Scholar] [CrossRef] [PubMed]
- Liu, N.; Sun, Y.-Y.; Zhang, X.-W.; Chen, S.; Wang, Y.; Zhang, Z.-X.; Song, S.-W.; Qiu, G.-B.; Fu, W.-N. Oncogenic miR-23a in Pancreatic Ductal Adenocarcinogenesis Via Inhibiting APAF1. Dig. Dis. Sci. 2015, 60, 2000–2008. [Google Scholar] [CrossRef] [PubMed]
- Wu, G.; Li, Z.; Jiang, P.; Zhang, X.; Xu, Y.; Chen, K.; Li, X. MicroRNA-23a promotes pancreatic cancer metastasis by targeting epithelial splicing regulator protein 1. Oncotarget 2017, 8, 82854–82871. [Google Scholar] [CrossRef]
- Lu, J.; Yang, Y.; Liu, X.; Chen, X.; Song, W.; Liu, Z. FTO-mediated LINC01134 stabilization to promote chemoresistance through miR-140-3p/WNT5A/WNT pathway in PDAC. Cell Death Dis. 2023, 14, 713. [Google Scholar] [CrossRef]
- Wei, X.; Wang, W.; Wang, L.; Zhang, Y.; Zhang, X.; Chen, M.; Wang, F.; Yu, J.; Ma, Y.; Sun, G. MicroRNA-21 induces 5-fluorouracil resistance in human pancreatic cancer cells by regulating PTEN and PDCD4. Cancer Med. 2016, 5, 693–702. [Google Scholar] [CrossRef]
- Wang, W.; Zhao, L.; Wei, X.; Wang, L.; Liu, S.; Yang, Y.; Wang, F.; Sun, G.; Zhang, J.; Ma, Y.; et al. MicroRNA-320a promotes 5-FU resistance in human pancreatic cancer cells. Sci. Rep. 2016, 6, 27641. [Google Scholar] [CrossRef]
- Zhao, L.; Zou, D.; Wei, X.; Wang, L.; Zhang, Y.; Liu, S.; Si, Y.; Zhao, H.; Wang, F.; Yu, J.; et al. MiRNA-221-3p desensitizes pancreatic cancer cells to 5-fluorouracil by targeting RB1. Tumor Biol. 2016, 37, 16053–16063. [Google Scholar] [CrossRef]
- Meng, Q.; Liang, C.; Hua, J.; Zhang, B.; Liu, J.; Zhang, Y.; Wei, M.; Yu, X.; Xu, J.; Shi, S. A miR-146a-5p/TRAF6/NF-kB p65 axis regulates pancreatic cancer chemoresistance: Functional validation and clinical significance. Theranostics 2020, 10, 3967–3979. [Google Scholar] [CrossRef]
- Yan, H.-J.; Liu, W.-S.; Sun, W.-H.; Wu, J.; Ji, M.; Wang, Q.; Zheng, X.; Jiang, J.-T.; Wu, C.-P. miR-17-5p Inhibitor Enhances Chemosensitivity to Gemcitabine Via Upregulating Bim Expression in Pancreatic Cancer Cells. Dig. Dis. Sci. 2012, 57, 3160–3167. [Google Scholar] [CrossRef]
- Xia, X.; Zhang, K.; Luo, G.; Cen, G.; Cao, J.; Huang, K.; Qiu, Z. Downregulation of miR-301a-3p sensitizes pancreatic cancer cells to gemcitabine treatment via PTEN. Am. J. Transl. Res. 2017, 9, 1886–1895. [Google Scholar]
- Wei, L.; Sun, J.; Wang, X.; Huang, Y.; Huang, L.; Han, L.; Zheng, Y.; Xu, Y.; Zhang, N.; Yang, M. Noncoding RNAs: An emerging modulator of drug resistance in pancreatic cancer. Front. Cell Dev. Biol. 2023, 11, 1226639. [Google Scholar] [CrossRef] [PubMed]
- Gu, L.; Zhang, J.; Shi, M.; Peng, C. The effects of miRNA-1180 on suppression of pancreatic cancer. Am. J. Transl. Res. 2017, 9, 2798–2806. [Google Scholar] [PubMed]
- Fu, Y.; Liu, S.; Zeng, S.; Shen, H. The critical roles of activated stellate cells-mediated paracrine signaling, metabolism and onco-immunology in pancreatic ductal adenocarcinoma. Mol. Cancer 2018, 17, 62. [Google Scholar] [CrossRef] [PubMed]
- Lonardo, E.; Frias-Aldeguer, J.; Hermann, P.C.; Heeschen, C. Pancreatic stellate cells form a niche for cancer stem cells and promote their self-renewal and invasiveness. Cell Cycle 2012, 11, 1282–1290. [Google Scholar] [CrossRef]
- Ji, Q.; Hao, X.; Zhang, M.; Tang, W.; Yang, M.; Li, L.; Xiang, D.; Desano, J.T.; Bommer, G.T.; Fan, D.; et al. MicroRNA miR-34 Inhibits Human Pancreatic Cancer Tumor-Initiating Cells. PLoS ONE 2009, 4, e6816. [Google Scholar] [CrossRef] [PubMed]
- Zhou, J.; Wang, H.; Che, J.; Xu, L.; Yang, W.; Li, Y.; Zhou, W. Silencing of microRNA-135b inhibits invasion, migration, and stemness of CD24+CD44+ pancreatic cancer stem cells through JADE-1-dependent AKT/mTOR pathway. Cancer Cell Int. 2020, 20, 134. [Google Scholar] [CrossRef] [PubMed]
- Zhou, B.; Sun, C.; Hu, X.; Zhan, H.; Zou, H.; Feng, Y.; Qiu, F.; Zhang, S.; Wu, L.; Zhang, B. MicroRNA-195 Suppresses the Progression of Pancreatic Cancer by Targeting DCLK1. Cell. Physiol. Biochem. 2017, 44, 1867–1881. [Google Scholar] [CrossRef]
- Guo, Q.S.; Wang, P.; Huang, Y.; Guo, Y.B.; Zhu, M.Y.; Xiong, Y.C. Regulatory effect of miR-30b on migration and invasion of pancreatic cancer stem cells. Zhonghua Yi Xue Za Zhi 2019, 99, 3019–3023. [Google Scholar] [CrossRef] [PubMed]
- Lu, Y.; Lu, J.; Li, X.; Zhu, H.; Fan, X.; Zhu, S.; Wang, Y.; Guo, Q.; Wang, L.; Huang, Y.; et al. MiR-200a inhibits epithelial-mesenchymal transition of pancreatic cancer stem cell. BMC Cancer 2014, 14, 85. [Google Scholar] [CrossRef]
- Chaudhary, A.K.; Mondal, G.; Kumar, V.; Kattel, K.; Mahato, R.I. Chemosensitization and inhibition of pancreatic cancer stem cell proliferation by overexpression of microRNA-205. Cancer Lett. 2017, 402, 1–8. [Google Scholar] [CrossRef]
- Hasegawa, S.; Eguchi, H.; Nagano, H.; Konno, M.; Tomimaru, Y.; Wada, H.; Hama, N.; Kawamoto, K.; Kobayashi, S.; Nishida, N.; et al. MicroRNA-1246 expression associated with CCNG2-mediated chemoresistance and stemness in pancreatic cancer. Br. J. Cancer 2014, 111, 1572–1580. [Google Scholar] [CrossRef]
- Li, Y.; Zhao, W.; Wang, Y.; Wang, H.; Liu, S. Extracellular vesicle-mediated crosstalk between pancreatic cancer and stromal cells in the tumor microenvironment. J. Nanobiotechnol. 2022, 20, 208. [Google Scholar] [CrossRef]
- Waldenmaier, M.; Seibold, T.; Seufferlein, T.; Eiseler, T. Pancreatic Cancer Small Extracellular Vesicles (Exosomes): A Tale of Short- and Long-Distance Communication. Cancers 2021, 13, 4844. [Google Scholar] [CrossRef]
- He, C.; Wang, L.; Li, L.; Zhu, G. Extracellular vesicle-orchestrated crosstalk between cancer-associated fibroblasts and tumors. Transl. Oncol. 2021, 14, 101231. [Google Scholar] [CrossRef] [PubMed]
- Batista, I.; Melo, S. Exosomes and the Future of Immunotherapy in Pancreatic Cancer. Int. J. Mol. Sci. 2019, 20, 567. [Google Scholar] [CrossRef] [PubMed]
- Zhou, M.; Chen, J.; Zhou, L.; Chen, W.; Ding, G.; Cao, L. Pancreatic cancer derived exosomes regulate the expression of TLR4 in dendritic cells via miR-203. Cell. Immunol. 2014, 292, 65–69. [Google Scholar] [CrossRef] [PubMed]
- Xie, Y.; Hang, Y.; Wang, Y.; Sleightholm, R.; Prajapati, D.R.; Bader, J.; Yu, A.; Tang, W.; Jaramillo, L.; Li, J.; et al. Stromal Modulation and Treatment of Metastatic Pancreatic Cancer with Local Intraperitoneal Triple miRNA/siRNA Nanotherapy. ACS Nano 2020, 14, 255–271. [Google Scholar] [CrossRef] [PubMed]
- Yang, T.; Han, Y.; Chen, J.; Liang, X.; Sun, L. MiR-506 Promotes Antitumor Immune Response in Pancreatic Cancer by Reprogramming Tumor-Associated Macrophages toward an M1 Phenotype. Biomedicines 2023, 11, 2874. [Google Scholar] [CrossRef] [PubMed]
- Felix, T.F.; Lopez Lapa, R.M.; De Carvalho, M.; Bertoni, N.; Tokar, T.; Oliveira, R.A.; M. Rodrigues, M.A.; Hasimoto, C.N.; Oliveira, W.K.; Pelafsky, L.; et al. MicroRNA modulated networks of adaptive and innate immune response in pancreatic ductal adenocarcinoma. PLoS ONE 2019, 14, e0217421. [Google Scholar] [CrossRef] [PubMed]
- Cook, M.E.; Jarjour, N.N.; Lin, C.C.; Edelson, B.T. Transcription Factor Bhlhe40 in Immunity and Autoimmunity. Trends Immunol. 2020, 41, 1023–1036. [Google Scholar] [CrossRef]
- Qi, W.; Liu, Q.; Fu, W.; Shi, J.; Shi, M.; Duan, S.; Li, Z.; Song, S.; Wang, J.; Liu, Y. BHLHE40, a potential immune therapy target, regulated by FGD5-AS1/miR-15a-5p in pancreatic cancer. Sci. Rep. 2023, 13, 16400. [Google Scholar] [CrossRef]
- Guo, S.; Fesler, A.; Wang, H.; Ju, J. microRNA based prognostic biomarkers in pancreatic Cancer. Biomark. Res. 2018, 6, 18. [Google Scholar] [CrossRef]
- Drakaki, A.; Iliopoulos, D. MicroRNA-gene signaling pathways in pancreatic cancer. Biomed. J. 2013, 36, 200–208. [Google Scholar] [CrossRef]
- Hu, W.; Liu, Q.; Pan, J.; Sui, Z. MiR-373-3p enhances the chemosensitivity of gemcitabine through cell cycle pathway by targeting CCND2 in pancreatic carcinoma cells. Biomed. Pharmacother. Biomed. Pharmacother. 2018, 105, 887–898. [Google Scholar] [CrossRef] [PubMed]
- Nakata, K.; Ohuchida, K.; Mizumoto, K.; Aishima, S.; Oda, Y.; Nagai, E.; Tanaka, M. Micro RNA-373 is Down-regulated in Pancreatic Cancer and Inhibits Cancer Cell Invasion. Ann. Surg. Oncol. 2014, 21, 564–574. [Google Scholar] [CrossRef] [PubMed]
- Nweke, E.; Brand, M. Downregulation of the let-7 family of microRNAs may promote insulin receptor/insulin-like growth factor signalling pathways in pancreatic ductal adenocarcinoma. Oncol. Lett. 2020, 20, 2613–2620. [Google Scholar] [CrossRef] [PubMed]
- Pai, P.; Rachagani, S.; Are, C.; Batra, S. Prospects of miRNA-Based Therapy for Pancreatic Cancer. Curr. Drug Targets 2013, 14, 1101–1109. [Google Scholar] [CrossRef] [PubMed]
- Zhao, G.; Wang, B.; Liu, Y.; Zhang, J.-G.; Deng, S.-C.; Qin, Q.; Tian, K.; Li, X.; Zhu, S.; Niu, Y.; et al. miRNA-141, Downregulated in Pancreatic Cancer, Inhibits Cell Proliferation and Invasion by Directly Targeting MAP4K4. Mol. Cancer Ther. 2013, 12, 2569–2580. [Google Scholar] [CrossRef] [PubMed]
- Tang, Y.; Tang, Y.; Cheng, Y.-S. miR-34a inhibits pancreatic cancer progression through Snail1-mediated epithelial–mesenchymal transition and the Notch signaling pathway. Sci. Rep. 2017, 7, 38232. [Google Scholar] [CrossRef] [PubMed]
- Long, K.; Zeng, Q.; Dong, W. The clinical significance of microRNA-409 in pancreatic carcinoma and associated tumor cellular functions. Bioengineered 2021, 12, 4633–4642. [Google Scholar] [CrossRef]
- Huang, X.; Lv, W.; Zhang, J.-H.; Lu, D.-L. miR-96 functions as a tumor suppressor gene by targeting NUAK1 in pancreatic cancer. Int. J. Mol. Med. 2014, 34, 1599–1605. [Google Scholar] [CrossRef]
- Yu, S.; Lu, Z.; Liu, C.; Meng, Y.; Ma, Y.; Zhao, W.; Liu, J.; Yu, J.; Chen, J. miRNA-96 Suppresses KRAS and Functions as a Tumor Suppressor Gene in Pancreatic Cancer. Cancer Res. 2010, 70, 6015–6025. [Google Scholar] [CrossRef]
- Chen, Q.; Wang, P.; Fu, Y.; Liu, X.; Xu, W.; Wei, J.; Gao, W.; Jiang, K.; Wu, J.; Miao, Y. MicroRNA-217 inhibits cell proliferation, invasion and migration by targeting Tpd52l2 in human pancreatic adenocarcinoma. Oncol. Rep. 2017, 38, 3567–3573. [Google Scholar] [CrossRef] [PubMed]
- Dutta, M.; Das, B.; Mohapatra, D.; Behera, P.; Senapati, S.; Roychowdhury, A. MicroRNA-217 modulates pancreatic cancer progression via targeting ATAD2. Life Sci. 2022, 301, 120592. [Google Scholar] [CrossRef] [PubMed]
- Yang, X.L.; Ma, Y.S.; Liu, Y.S.; Jiang, X.H.; Ding, H.; Shi, Y.; Jia, C.Y.; Lu, G.X.; Zhang, D.D.; Wang, H.M.; et al. microRNA-873 inhibits self-renewal and proliferation of pancreatic cancer stem cells through pleckstrin-2-dependent PI3K/AKT pathway. Cell. Signal. 2021, 84, 110025. [Google Scholar] [CrossRef] [PubMed]
- Mokhlis, H.A.; Bayraktar, R.; Kabil, N.N.; Caner, A.; Kahraman, N.; Rodriguez-Aguayo, C.; Zambalde, E.P.; Sheng, J.; Karagoz, K.; Kanlikilicer, P.; et al. The Modulatory Role of MicroRNA-873 in the Progression of KRAS-Driven Cancers. Mol. Ther. Nucleic Acids 2019, 14, 301–317. [Google Scholar] [CrossRef] [PubMed]
- Rencuzogulları, O.; Yerlikaya, P.O.; Gürkan, A.Ç.; Arısan, E.D.; Telci, D. Palbociclib negatively regulates fatty acid synthesis due to upregulation of AMPKα and miR-33a levels to increase apoptosis in Panc-1 and MiaPaCa-2 cells. Biotechnol. Appl. Biochem. 2022, 69, 342–354. [Google Scholar] [CrossRef] [PubMed]
- Su, X.; Lai, T.; Tao, Y.; Zhang, Y.; Zhao, C.; Zhou, J.; Chen, E.; Zhu, M.; Zhang, S.; Wang, B.; et al. miR-33a-3p regulates METTL3-mediated AREG stability and alters EMT to inhibit pancreatic cancer invasion and metastasis. Sci. Rep. 2023, 13, 13587. [Google Scholar] [CrossRef]
- Lian, Y.; Jiang, D.; Sun, J. Tumor suppressive role of miR-33a-5p in pancreatic ductal adenocarcinoma cells by directly targeting RAP2A. Cell. Mol. Biol. Lett. 2021, 26, 24. [Google Scholar] [CrossRef] [PubMed]
- Marin-Muller, C.; Li, D.; Bharadwaj, U.; Li, M.; Chen, C.; Hodges, S.E.; Fisher, W.E.; Mo, Q.; Hung, M.-C.; Yao, Q. A Tumorigenic Factor Interactome Connected through Tumor Suppressor MicroRNA-198 in Human Pancreatic Cancer. Clin. Cancer Res. 2013, 19, 5901–5913. [Google Scholar] [CrossRef]
- Zhou, X.; Liu, K.; Cui, J.; Xiong, J.; Wu, H.; Peng, T.; Guo, Y. Circ-MBOAT2 knockdown represses tumor progression and glutamine catabolism by miR-433-3p/GOT1 axis in pancreatic cancer. J. Exp. Clin. Cancer Res. 2021, 40, 124. [Google Scholar] [CrossRef]
- Zhao, Q.; Chen, S.; Zhu, Z.; Yu, L.; Ren, Y.; Jiang, M.; Weng, J.; Li, B. miR-21 promotes EGF-induced pancreatic cancer cell proliferation by targeting Spry2. Cell Death Dis. 2018, 9, 1157. [Google Scholar] [CrossRef]
- Hwang, J.-H.; Voortman, J.; Giovannetti, E.; Steinberg, S.M.; Leon, L.G.; Kim, Y.-T.; Funel, N.; Park, J.K.; Kim, M.A.; Kang, G.H.; et al. Identification of MicroRNA-21 as a Biomarker for Chemoresistance and Clinical Outcome Following Adjuvant Therapy in Resectable Pancreatic Cancer. PLoS ONE 2010, 5, e10630. [Google Scholar] [CrossRef] [PubMed]
- Giovannetti, E.; Funel, N.; Peters, G.J.; Del Chiaro, M.; Erozenci, L.A.; Vasile, E.; Leon, L.G.; Pollina, L.E.; Groen, A.; Falcone, A.; et al. MicroRNA-21 in Pancreatic Cancer: Correlation with Clinical Outcome and Pharmacologic Aspects Underlying Its Role in the Modulation of Gemcitabine Activity. Cancer Res. 2010, 70, 4528–4538. [Google Scholar] [CrossRef]
- Wu, X.; Huang, J.; Yang, Z.; Zhu, Y.; Zhang, Y.; Wang, J.; Yao, W. MicroRNA-221-3p is related to survival and promotes tumour progression in pancreatic cancer: A comprehensive study on functions and clinicopathological value. Cancer Cell Int. 2020, 20, 443. [Google Scholar] [CrossRef]
- Song, J.; Ouyang, Y.; Che, J.; Li, X.; Zhao, Y.; Yang, K.; Zhao, X.; Chen, Y.; Fan, C.; Yuan, W. Potential Value of miR-221/222 as Diagnostic, Prognostic, and Therapeutic Biomarkers for Diseases. Front. Immunol. 2017, 8, 56. [Google Scholar] [CrossRef]
- Ryu, J.K.; Hong, S.-M.; Karikari, C.A.; Hruban, R.H.; Goggins, M.G.; Maitra, A. Aberrant MicroRNA-155 Expression Is an Early Event in the Multistep Progression of Pancreatic Adenocarcinoma. Pancreatology 2010, 10, 66–73. [Google Scholar] [CrossRef] [PubMed]
- Shang, D.; Xie, C.; Hu, J.; Tan, J.; Yuan, Y.; Liu, Z.; Yang, Z. Pancreatic cancer cell–derived exosomal microRNA-27a promotes angiogenesis of human microvascular endothelial cells in pancreatic cancer via BTG2. J. Cell. Mol. Med. 2020, 24, 588–604. [Google Scholar] [CrossRef] [PubMed]
- Cui, Z.; Liu, G.; Kong, D. miRNA-27a promotes the proliferation and inhibits apoptosis of human pancreatic cancer cells by Wnt/β-catenin pathway. Oncol. Rep. 2017, 39, 755–763. [Google Scholar] [CrossRef] [PubMed]
- Huang, F.; Tang, J.; Zhuang, X.; Zhuang, Y.; Cheng, W.; Chen, W.; Yao, H.; Zhang, S. MiR-196a Promotes Pancreatic Cancer Progression by Targeting Nuclear Factor Kappa-B-Inhibitor Alpha. PLoS ONE 2014, 9, e87897. [Google Scholar] [CrossRef] [PubMed]
- Wang, C.; Li, X.; Zhang, L.; Chen, Y.; Dong, R.; Zhang, J.; Zhao, J.; Guo, X.; Yang, G.; Li, Y.; et al. miR-194-5p down-regulates tumor cell PD-L1 expression and promotes anti-tumor immunity in pancreatic cancer. Int. Immunopharmacol. 2021, 97, 107822. [Google Scholar] [CrossRef] [PubMed]
- Zhang, J.; Zhao, C.-Y.; Zhang, S.-H.; Yu, D.-H.; Chen, Y.; Liu, Q.-H.; Shi, M.; Ni, C.-R.; Zhu, M.-H. Upregulation of miR-194 contributes to tumor growth and progression in pancreatic ductal adenocarcinoma. Oncol. Rep. 2014, 31, 1157–1164. [Google Scholar] [CrossRef] [PubMed]
- Park, J.-K.; Henry, J.C.; Jiang, J.; Esau, C.; Gusev, Y.; Lerner, M.R.; Postier, R.G.; Brackett, D.J.; Schmittgen, T.D. miR-132 and miR-212 are increased in pancreatic cancer and target the retinoblastoma tumor suppressor. Biochem. Biophys. Res. Commun. 2011, 406, 518–523. [Google Scholar] [CrossRef]
- Sun, X.-J.; Liu, B.-Y.; Yan, S.; Jiang, T.-H.; Cheng, H.-Q.; Jiang, H.-S.; Cao, Y.; Mao, A.-W. MicroRNA-29a Promotes Pancreatic Cancer Growth by Inhibiting Tristetraprolin. Cell. Physiol. Biochem. 2015, 37, 707–718. [Google Scholar] [CrossRef] [PubMed]
- Song, Z.; Ren, H.; Gao, S.; Zhao, X.; Zhang, H.; Hao, J. The clinical significance and regulation mechanism of hypoxia-inducible factor-1 and miR-191 expression in pancreatic cancer. Tumor Biol. 2014, 35, 11319–11328. [Google Scholar] [CrossRef] [PubMed]
- Liu, H.; Xu, X.-F.; Zhao, Y.; Tang, M.-C.; Zhou, Y.-Q.; Lu, J.; Gao, F.-H. MicroRNA-191 promotes pancreatic cancer progression by targeting USP10. Tumor Biol. 2014, 35, 12157–12163. [Google Scholar] [CrossRef] [PubMed]
- Diao, H.; Ye, Z.; Qin, R. miR-23a acts as an oncogene in pancreatic carcinoma by targeting FOXP2. J. Investig. Med. 2018, 66, 676–683. [Google Scholar] [CrossRef] [PubMed]
- Chao, J.; Jin, L.; Zhang, X.; Ding, D.; Wu, S.; Ma, L.; Zhu, B.; Shan, S.; Yun, X.; Gao, P.; et al. Insight into the effects of microRNA-23a-3p on pancreatic cancer and its underlying molecular mechanism. Oncol. Lett. 2020, 19, 187–194. [Google Scholar] [CrossRef] [PubMed]
- Li, J.; Wu, H.; Li, W.; Yin, L.; Guo, S.; Xu, X.; Ouyang, Y.; Zhao, Z.; Liu, S.; Tian, Y.; et al. Downregulated miR-506 expression facilitates pancreatic cancer progression and chemoresistance via SPHK1/Akt/NF-κB signaling. Oncogene 2016, 35, 5501–5514. [Google Scholar] [CrossRef] [PubMed]
- Cheng, R.-F.; Wang, J.; Zhang, J.-Y.; Sun, L.; Zhao, Y.-R.; Qiu, Z.-Q.; Sun, B.-C.; Sun, Y. MicroRNA-506 is up-regulated in the development of pancreatic ductal adenocarcinoma and is associated with attenuated disease progression. Chin. J. Cancer 2016, 35, 64. [Google Scholar] [CrossRef]
- Hashemi, A.; Gorji-Bahri, G. MicroRNA: Promising Roles in Cancer Therapy. Curr. Pharm. Biotechnol. 2020, 21, 1186–1203. [Google Scholar] [CrossRef]
- Liu, C.; Cheng, H.; Shi, S.; Cui, X.; Yang, J.; Chen, L.; Cen, P.; Cai, X.; Lu, Y.; Wu, C.; et al. MicroRNA-34b inhibits pancreatic cancer metastasis through repressing Smad3. Curr. Mol. Med. 2013, 13, 467–478. [Google Scholar] [CrossRef]
- Li, W.; Wang, Y.; Liu, R.; Kasinski, A.L.; Shen, H.; Slack, F.J.; Tang, D.G. MicroRNA-34a: Potent Tumor Suppressor, Cancer Stem Cell Inhibitor, and Potential Anticancer Therapeutic. Front. Cell Dev. Biol. 2021, 9, 640587. [Google Scholar] [CrossRef]
- Gurbuz, N.; Ozpolat, B. MicroRNA-based Targeted Therapeutics in Pancreatic Cancer. Anticancer. Res. 2019, 39, 529–532. [Google Scholar] [CrossRef] [PubMed]
- Zhan, T.; Zhu, Q.; Han, Z.; Tan, J.; Liu, M.; Liu, W.; Chen, W.; Chen, X.; Chen, X.; Deng, J.; et al. miR-455-3p Functions as a Tumor Suppressor by Restraining Wnt/β-Catenin Signaling via TAZ in Pancreatic Cancer. Cancer Manag. Res. 2020, 12, 1483–1492. [Google Scholar] [CrossRef] [PubMed]
- Shen, J.; Wan, R.; Hu, G.; Yang, L.; Xiong, J.; Wang, F.; Shen, J.; He, S.; Guo, X.; Ni, J.; et al. miR-15b and miR-16 induce the apoptosis of rat activated pancreatic stellate cells by targeting Bcl-2 in vitro. Pancreatol. Off. J. Int. Assoc. Pancreatol. (IAP) 2012, 12, 91–99. [Google Scholar] [CrossRef] [PubMed]
- Kent, O.A.; Chivukula, R.R.; Mullendore, M.; Wentzel, E.A.; Feldmann, G.; Lee, K.H.; Liu, S.; Leach, S.D.; Maitra, A.; Mendell, J.T. Repression of the miR-143/145 cluster by oncogenic Ras initiates a tumor-promoting feed-forward pathway. Genes Dev. 2010, 24, 2754–2759. [Google Scholar] [CrossRef] [PubMed]
- Karmakar, S.; Kaushik, G.; Nimmakayala, R.; Rachagani, S.; Ponnusamy, M.P.; Batra, S.K. MicroRNA regulation of K-Ras in pancreatic cancer and opportunities for therapeutic intervention. Semin. Cancer Biol. 2019, 54, 63–71. [Google Scholar] [CrossRef]
- Srivastava, S.K.; Bhardwaj, A.; Singh, S.; Arora, S.; Wang, B.; Grizzle, W.E.; Singh, A.P. MicroRNA-150 directly targets MUC4 and suppresses growth and malignant behavior of pancreatic cancer cells. Carcinogenesis 2011, 32, 1832–1839. [Google Scholar] [CrossRef]
- Tesfaye, A.A.; Azmi, A.S.; Philip, P.A. miRNA and Gene Expression in Pancreatic Ductal Adenocarcinoma. Am. J. Pathol. 2019, 189, 58–70. [Google Scholar] [CrossRef]
- Kamali, M.J.; Salehi, M.; Fatemi, S.; Moradi, F.; Khoshghiafeh, A.; Ahmadifard, M. Locked nucleic acid (LNA): A modern approach to cancer diagnosis and treatment. Exp. Cell Res. 2023, 423, 113442. [Google Scholar] [CrossRef]
- Lima, J.F.; Cerqueira, L.; Figueiredo, C.; Oliveira, C.; Azevedo, N.F. Anti-miRNA oligonucleotides: A comprehensive guide for design. RNA Biol. 2018, 15, 338–352. [Google Scholar] [CrossRef]
- Griveau, A.; Bejaud, J.; Anthiya, S.; Avril, S.; Autret, D.; Garcion, E. Silencing of miR-21 by locked nucleic acid-lipid nanocapsule complexes sensitize human glioblastoma cells to radiation-induced cell death. Int. J. Pharm. 2013, 454, 765–774. [Google Scholar] [CrossRef]
- Ma, L.; Reinhardt, F.; Pan, E.; Soutschek, J.; Bhat, B.; Marcusson, E.G.; Teruya-Feldstein, J.; Bell, G.W.; Weinberg, R.A. Therapeutic silencing of miR-10b inhibits metastasis in a mouse mammary tumor model. Nat. Biotechnol. 2010, 28, 341–347. [Google Scholar] [CrossRef] [PubMed]
- Lee, T.-Y.; Tseng, C.-J.; Wang, J.-W.; Wu, C.-P.; Chung, C.-Y.; Tseng, T.-T.; Lee, S.-C. Anti-microRNA-1976 as a Novel Approach to Enhance Chemosensitivity in XAF1+ Pancreatic and Liver Cancer. Biomedicines 2023, 11, 1136. [Google Scholar] [CrossRef] [PubMed]
- Li, X.; Xu, H.; Yi, J.; Dong, C.; Zhang, H.; Wang, Z.; Miao, L.; Zhou, W. miR-365 secreted from M2 Macrophage-derived extracellular vesicles promotes pancreatic ductal adenocarcinoma progression through the BTG2/FAK/AKT axis. J. Cell. Mol. Med. 2021, 25, 4671–4683. [Google Scholar] [CrossRef]
- Lavenniah, A.; Luu, T.D.A.; Li, Y.P.; Lim, T.B.; Jiang, J.; Ackers-Johnson, M.; Foo, R.S.Y. Engineered Circular RNA Sponges Act as miRNA Inhibitors to Attenuate Pressure Overload-Induced Cardiac Hypertrophy. Mol. Ther. 2020, 28, 1506–1517. [Google Scholar] [CrossRef] [PubMed]
- Rama, A.R.; Quiñonero, F.; Mesas, C.; Melguizo, C.; Prados, J. Synthetic Circular miR-21 Sponge as Tool for Lung Cancer Treatment. Int. J. Mol. Sci. 2022, 23, 2963. [Google Scholar] [CrossRef]
- Han, J.; Yang, Z.; Zhao, S.; Zheng, L.; Tian, Y.; Lv, Y. Circ_0027599 elevates RUNX1 expression via sponging miR-21-5p on gastric cancer progression. Eur. J. Clin. Investig. 2021, 51, e13592. [Google Scholar] [CrossRef]
- Liu, Y.; Li, X.; Zhu, S.; Zhang, J.G.; Yang, M.; Qin, Q.; Deng, S.C.; Wang, B.; Tian, K.; Liu, L.; et al. Ectopic expression of miR-494 inhibited the proliferation, invasion and chemoresistance of pancreatic cancer by regulating SIRT1 and c-Myc. Gene Ther. 2015, 22, 729–738. [Google Scholar] [CrossRef] [PubMed]
- Yu, C.; Wang, M.; Li, Z.; Xiao, J.; Peng, F.; Guo, X.; Deng, Y.; Jiang, J.; Sun, C. MicroRNA-138-5p regulates pancreatic cancer cell growth through targeting FOXC1. Cell. Oncol. 2015, 38, 173–181. [Google Scholar] [CrossRef]
- Cioffi, M.; Trabulo, S.M.; Sanchez-Ripoll, Y.; Miranda-Lorenzo, I.; Lonardo, E.; Dorado, J.; Reis Vieira, C.; Ramirez, J.C.; Hidalgo, M.; Aicher, A.; et al. The miR-17-92 cluster counteracts quiescence and chemoresistance in a distinct subpopulation of pancreatic cancer stem cells. Gut 2015, 64, 1936–1948. [Google Scholar] [CrossRef]
- Amponsah, P.S.; Fan, P.; Bauer, N.; Zhao, Z.; Gladkich, J.; Fellenberg, J.; Herr, I. microRNA-210 overexpression inhibits tumor growth and potentially reverses gemcitabine resistance in pancreatic cancer. Cancer Lett. 2017, 388, 107–117. [Google Scholar] [CrossRef]
- Tan, G.; Wu, L.; Tan, J.; Zhang, B.; Tai, W.C.-S.; Xiong, S.; Chen, W.; Yang, J.; Li, H. MiR-1180 promotes apoptotic resistance to human hepatocellular carcinoma via activation of NF-κB signaling pathway. Sci. Rep. 2016, 6, 22328. [Google Scholar] [CrossRef] [PubMed]
- Li, Z.; Li, X.; Yu, C.; Wang, M.; Peng, F.; Xiao, J.; Tian, R.; Jiang, J.; Sun, C. MicroRNA-100 regulates pancreatic cancer cells growth and sensitivity to chemotherapy through targeting FGFR3. Tumor Biol. 2014, 35, 11751–11759. [Google Scholar] [CrossRef] [PubMed]
- Sun, D.; Wang, X.; Sui, G.; Chen, S.; Yu, M.; Zhang, P. Downregulation of miR-374b-5p promotes chemotherapeutic resistance in pancreatic cancer by upregulating multiple anti-apoptotic proteins. Int. J. Oncol. 2018, 52, 1491–1503. [Google Scholar] [CrossRef]
- Wang, Z.C.; Huang, F.Z.; Xu, H.B.; Sun, J.C.; Wang, C.F. MicroRNA-137 inhibits autophagy and chemosensitizes pancreatic cancer cells by targeting ATG5. Int. J. Biochem. Cell Biol. 2019, 111, 63–71. [Google Scholar] [CrossRef] [PubMed]
- Kara, G.; Arun, B.; Calin, G.A.; Ozpolat, B. miRacle of microRNA-Driven Cancer Nanotherapeutics. Cancers 2022, 14, 3818. [Google Scholar] [CrossRef]
- Carotenuto, P.; Amato, F.; Lampis, A.; Rae, C.; Hedayat, S.; Previdi, M.C.; Zito, D.; Raj, M.; Guzzardo, V.; Sclafani, F.; et al. Modulation of pancreatic cancer cell sensitivity to FOLFIRINOX through microRNA-mediated regulation of DNA damage. Nat. Commun. 2021, 12, 6738. [Google Scholar] [CrossRef]
- Yuen, J.G.; Fesler, A.; Hwang, G.-R.; Chen, L.-B.; Ju, J. Development of 5-FU-modified tumor suppressor microRNAs as a platform for novel microRNA-based cancer therapeutics. Mol. Ther. 2022, 30, 3450–3461. [Google Scholar] [CrossRef]
- Almanzar, V.M.D.; Shah, K.; Lacomb, J.F.; Mojumdar, A.; Patel, H.R.; Cheung, J.; Tang, M.; Ju, J.; Bialkowska, A.B. 5-FU-miR-15a Inhibits Activation of Pancreatic Stellate Cells by Reducing YAP1 and BCL-2 Levels In Vitro. Int. J. Mol. Sci. 2023, 24, 3954. [Google Scholar] [CrossRef]
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Pal, A.; Ojha, A.; Ju, J. Functional and Potential Therapeutic Implication of MicroRNAs in Pancreatic Cancer. Int. J. Mol. Sci. 2023, 24, 17523. https://doi.org/10.3390/ijms242417523
Pal A, Ojha A, Ju J. Functional and Potential Therapeutic Implication of MicroRNAs in Pancreatic Cancer. International Journal of Molecular Sciences. 2023; 24(24):17523. https://doi.org/10.3390/ijms242417523
Chicago/Turabian StylePal, Amartya, Anushka Ojha, and Jingfang Ju. 2023. "Functional and Potential Therapeutic Implication of MicroRNAs in Pancreatic Cancer" International Journal of Molecular Sciences 24, no. 24: 17523. https://doi.org/10.3390/ijms242417523