Mir-153-3p Modulates the Breast Cancer Cells’ Chemosensitivity to Doxorubicin by Targeting KIF20A
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Transfection of Cells
2.2. Response of Doxorubicin Chemosensitivity against miR-153-3p
2.3. Immunofluorescence of Ki67 and CD63
2.4. Dual Luciferase Reporter Assay
2.5. Cell Migration and Invasion Assays
2.6. Flow Cytometry of Apoptosis and Cell Cycle Arrest
2.7. Detection of Proteins through Western Blot
2.8. Tumorigenicity in Nude Mice
2.9. Statistical Analysis
3. Results
3.1. Doxorubicin-Sensitive Breast Cancer Cells Are Caused by the Overexpression of miR-153-3p
3.2. Effects of miR-153-3p and Doxorubicin on Ki67 Expression
3.3. KIF20A Is a Direct Target Gene of miR-153-3p and Is Inhibited by miR-153-3p and Doxorubicin
3.4. Overexpression of miR-153-3p Enhances Doxorubicin-Induced Apoptosis
3.5. Effects of miR-153-3p on Cell Migration and Invasion
3.6. Effect of miR-153-3p on Cell Cycle
3.7. Effects of miR-153-3p Mimics on Intracellular Vesicle Packaging
3.8. miR-153-3p Increases the Chemosensitivity of Dox In Vivo
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Mehrgou, A.; Akouchekian, M. The importance of BRCA1 and BRCA2 genes mutations in breast cancer development. Med. J. Islam. Repub. Iran 2016, 30, 369. [Google Scholar] [PubMed]
- Fahad Ullah, M. Breast cancer: Current perspectives on the disease status. In Breast cancer Metastasis and Drug Resistance: Challenges and Progress; Springer: Berlin/Heidelberg, Germany, 2019; pp. 51–64. [Google Scholar]
- Iqbal, N.; Iqbal, N. Human epidermal growth factor receptor 2 (HER2) in cancers: Overexpression and therapeutic implications. Mol. Biol. Int. 2014, 2014, 852748. [Google Scholar] [CrossRef] [PubMed]
- de Savornin Lohman, E.; de Bitter, T.; Verhoeven, R.; van der Geest, L.; Hagendoorn, J.; Haj Mohammad, N.; Daams, F.; Klümpen, H.-J.; van Gulik, T.; Erdmann, J. Trends in treatment and survival of gallbladder cancer in the Netherlands; identifying gaps and opportunities from a nation-wide cohort. Cancers 2020, 12, 918. [Google Scholar] [CrossRef] [Green Version]
- Lovitt, C.J.; Shelper, T.B.; Avery, V.M. Doxorubicin resistance in breast cancer cells is mediated by extracellular matrix proteins. BMC Cancer 2018, 18, 1–11. [Google Scholar] [CrossRef] [Green Version]
- Marinello, J.; Delcuratolo, M.; Capranico, G. Anthracyclines as topoisomerase II poisons: From early studies to new perspectives. Int. J. Mol. Sci. 2018, 19, 3480. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Skok, Z.; Zidar, N.; Kikelj, D.; Ilaš, J. Dual inhibitors of human DNA topoisomerase II and other cancer-related targets. J. Med. Chem. 2019, 63, 884–904. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kubiliūtė, R.; Šulskytė, I.; Daniūnaitė, K.; Daugelavičius, R.; Jarmalaitė, S. Molecular features of doxorubicin-resistance development in colorectal cancer CX-1 cell line. Medicina 2016, 52, 298–306. [Google Scholar] [CrossRef] [PubMed]
- 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]
- Zhang, W.; Mao, S.; Shi, D.; Zhang, J.; Zhang, Z.; Guo, Y.; Wu, Y.; Wang, R.; Wang, L.; Huang, Y. MicroRNA-153 decreases tryptophan catabolism and inhibits angiogenesis in bladder cancer by targeting indoleamine 2,3-dioxygenase 1. Front. Oncol. 2019, 9, 619. [Google Scholar] [CrossRef]
- Wang, L.; Lv, X.; Fu, X.; Su, L.; Yang, T.; Xu, P. MiR-153 inhibits the resistance of lung cancer to gefitinib via modulating expression of ABCE1. Cancer Biomark. 2019, 25, 361–369. [Google Scholar] [CrossRef] [PubMed]
- Yuan, Y.; Du, W.; Wang, Y.; Xu, C.; Wang, J.; Zhang, Y.; Wang, H.; Ju, J.; Zhao, L.; Wang, Z. Suppression of AKT expression by mi R-153 produced anti-tumor activity in lung cancer. Int. J. Cancer 2015, 136, 1333–1340. [Google Scholar] [CrossRef] [PubMed]
- Ghasemi, A.; Fallah, S.; Ansari, M. MiR-153 as a Tumor Suppressor in Glioblastoma Multiforme is Downregulated by DNA Methylation. Clin. Lab. 2016, 62, 573–580. [Google Scholar] [CrossRef]
- Wu, X.; Li, L.; Li, Y.; Liu, Z. MiR-153 promotes breast cancer cell apoptosis by targeting HECTD3. Am. J. Cancer Res. 2016, 6, 1563. [Google Scholar]
- Zuo, Z.; Ye, F.; Liu, Z.; Huang, J.; Gong, Y. MicroRNA-153 inhibits cell proliferation, migration, invasion and epithelial-mesenchymal transition in breast cancer via direct targeting of RUNX2. Exp. Ther. Med. 2019, 17, 4693–4702. [Google Scholar] [CrossRef] [Green Version]
- Zhang, X.; Yu, J.; Zhao, C.; Ren, H.; Yuan, Z.; Zhang, B.; Zhuang, J.; Wang, J.; Feng, B. MiR-181b-5p modulates chemosensitivity of glioma cells to temozolomide by targeting Bcl-2. Biomed. Pharmacother. 2019, 109, 2192–2202. [Google Scholar] [CrossRef]
- Peng, G.; Hakim, M.; Broza, Y.; Billan, S.; Abdah-Bortnyak, R.; Kuten, A.; Tisch, U.; Haick, H. Detection of lung, breast, colorectal, and prostate cancers from exhaled breath using a single array of nanosensors. Br. J. Cancer 2010, 103, 542–551. [Google Scholar] [CrossRef]
- Mbemi, A.; Khanna, S.; Njiki, S.; Yedjou, C.G.; Tchounwou, P.B. Impact of gene–environment interactions on cancer development. Int. J. Environ. Res. Public Health 2020, 17, 8089. [Google Scholar] [CrossRef] [PubMed]
- O’Brien, K.; Ried, K.; Binjemain, T.; Sali, A. Integrative Approaches to the Treatment of Cancer. Cancers 2022, 14, 5933. [Google Scholar] [CrossRef]
- Lu, L.; Ju, F.; Zhao, H.; Ma, X. MicroRNA-134 modulates resistance to doxorubicin in human breast cancer cells by downregulating ABCC1. Biotechnol. Lett. 2015, 37, 2387–2394. [Google Scholar] [CrossRef] [PubMed]
- Yu, P.; Yu, H.; Guo, C.; Cui, Z.; Chen, X.; Yin, Q.; Zhang, P.; Yang, X.; Cui, H.; Li, Y. Reversal of doxorubicin resistance in breast cancer by mitochondria-targeted pH-responsive micelles. Acta Biomater. 2015, 14, 115–124. [Google Scholar] [CrossRef]
- Magnani, L.; Stoeck, A.; Zhang, X.; Lánczky, A.; Mirabella, A.C.; Wang, T.-L.; Gyorffy, B.; Lupien, M. Genome-wide reprogramming of the chromatin landscape underlies endocrine therapy resistance in breast cancer. Proc. Natl. Acad. Sci. USA 2013, 110, E1490–E1499. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Marquette, C.; Nabell, L. Chemotherapy-resistant metastatic breast cancer. Curr. Treat. Options Oncol. 2012, 13, 263–275. [Google Scholar] [CrossRef] [PubMed]
- Islam, F.; Gopalan, V.; Smith, R.A.; Lam, A.K.-Y. Translational potential of cancer stem cells: A review of the detection of cancer stem cells and their roles in cancer recurrence and cancer treatment. Exp. Cell Res. 2015, 335, 135–147. [Google Scholar] [CrossRef] [PubMed]
- Al-Malky, H.S.; Al Harthi, S.E.; Osman, A.-M.M. Major obstacles to doxorubicin therapy: Cardiotoxicity and drug resistance. J. Oncol. Pharm. Pract. 2020, 26, 434–444. [Google Scholar] [CrossRef]
- Kumar, U.; Hu, Y.; Masrour, N.; Castellanos-Uribe, M.; Harrod, A.; May, S.T.; Ali, S.; Speirs, V.; Coombes, R.C.; Yagüe, E. MicroRNA-495/TGF-β/FOXC1 axis regulates multidrug resistance in metaplastic breast cancer cells. Biochem. Pharmacol. 2021, 192, 114692. [Google Scholar] [CrossRef]
- Zhang, Y.; Wang, J. MicroRNAs are important regulators of drug resistance in colorectal cancer. Biol. Chem. 2017, 398, 929–938. [Google Scholar] [CrossRef] [Green Version]
- Pogribny, I.P.; Filkowski, J.N.; Tryndyak, V.P.; Golubov, A.; Shpyleva, S.I.; Kovalchuk, O. Alterations of microRNAs and their targets are associated with acquired resistance of MCF-7 breast cancer cells to cisplatin. Int. J. Cancer 2010, 127, 1785–1794. [Google Scholar] [CrossRef]
- Lu, X.; Liu, R.; Wang, M.; Kumar, A.K.; Pan, F.; He, L.; Hu, Z.; Guo, Z. MicroRNA-140 impedes DNA repair by targeting FEN1 and enhances chemotherapeutic response in breast cancer. Oncogene 2020, 39, 234–247. [Google Scholar] [CrossRef]
- Long, J.; Ji, Z.; Jiang, K.; Wang, Z.; Meng, G. miR-193b modulates resistance to doxorubicin in human breast cancer cells by downregulating MCL-1. BioMed Res. Int. 2015, 2015, 373574. [Google Scholar] [CrossRef]
- Gao, M.; Miao, L.; Liu, M.; Li, C.; Yu, C.; Yan, H.; Yin, Y.; Wang, Y.; Qi, X.; Ren, J. miR-145 sensitizes breast cancer to doxorubicin by targeting multidrug resistance-associated protein-1. Oncotarget 2016, 7, 59714. [Google Scholar] [CrossRef] [Green Version]
- Li, Z.; Chen, C.; Chen, L.; Hu, D.; Yang, X.; Zhuo, W.; Chen, Y.; Yang, J.; Zhou, Y.; Mao, M. STAT5a confers doxorubicin resistance to breast cancer by regulating ABCB1. Front. Oncol. 2021, 2761, 697950. [Google Scholar] [CrossRef]
- Miserey-Lenkei, S.; Bousquet, H.; Pylypenko, O.; Bardin, S.; Dimitrov, A.; Bressanelli, G.; Bonifay, R.; Fraisier, V.; Guillou, C.; Bougeret, C. Coupling fission and exit of RAB6 vesicles at Golgi hotspots through kinesin-myosin interactions. Nat. Commun. 2017, 8, 1254. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mandal, K.; Pogoda, K.; Nandi, S.; Mathieu, S.; Kasri, A.; Klein, E.; Radvanyi, F.; Goud, B.; Janmey, P.A.; Manneville, J.-B. Role of a kinesin motor in cancer cell mechanics. Nano Lett. 2019, 19, 7691–7702. [Google Scholar] [CrossRef] [PubMed]
- Sullivan, C.; Liu, Y.; Shen, J.; Curtis, A.; Newman, C.; Hock, J.M.; Li, X. Novel interactions between FOXM1 and CDC25A regulate the cell cycle. PLoS ONE 2012, 7, e51277. [Google Scholar] [CrossRef] [Green Version]
- Khongkow, P.; Gomes, A.; Gong, C.; Man, E.; Tsang, J.W.; Zhao, F.; Monteiro, L.; Coombes, R.; Medema, R.; Khoo, U. Paclitaxel targets FOXM1 to regulate KIF20A in mitotic catastrophe and breast cancer paclitaxel resistance. Oncogene 2016, 35, 990–1002. [Google Scholar] [CrossRef] [Green Version]
- Shen, T.; Yang, L.; Zhang, Z.; Yu, J.; Dai, L.; Gao, M.; Shang, Z.; Niu, Y. KIF20A affects the prognosis of bladder cancer by promoting the proliferation and metastasis of bladder cancer cells. Dis. Mrk. 2019, 2019, 4863182. [Google Scholar] [CrossRef] [Green Version]
- Xiong, M.; Zhuang, K.; Luo, Y.; Lai, Q.; Luo, X.; Fang, Y.; Zhang, Y.; Li, A.; Liu, S. KIF20A promotes cellular malignant behavior and enhances resistance to chemotherapy in colorectal cancer through regulation of the JAK/STAT3 signaling pathway. Aging 2019, 11, 11905. [Google Scholar] [CrossRef] [PubMed]
- Xie, F.; He, C.; Gao, S.; Yang, Z.; Li, L.; Qiao, L.; Fang, L. Retracted: KIF20A silence inhibits the migration, invasion and proliferation of non-small cell lung cancer and regulates the JNK pathway. Clin. Exp. Pharmacol. Physiol. 2020, 47, 135–142. [Google Scholar] [CrossRef] [PubMed]
- Zhen, Y.; Stenmark, H. Cellular functions of Rab GTPases at a glance. J. Cell Sci. 2015, 128, 3171–3176. [Google Scholar] [CrossRef] [Green Version]
- Binotti, B.; Pavlos, N.J.; Riedel, D.; Wenzel, D.; Vorbrüggen, G.; Schalk, A.M.; Kühnel, K.; Boyken, J.; Erck, C.; Martens, H. The GTPase Rab26 links synaptic vesicles to the autophagy pathway. Elife 2015, 4, e05597. [Google Scholar] [CrossRef] [PubMed]
- Dong, W.; He, B.; Qian, H.; Liu, Q.; Wang, D.; Li, J.; Wei, Z.; Wang, Z.; Xu, Z.; Wu, G. RAB26-dependent autophagy protects adherens junctional integrity in acute lung injury. Autophagy 2018, 14, 1677–1692. [Google Scholar] [CrossRef] [PubMed]
- Jin, R.U.; Mills, J.C. RAB26 coordinates lysosome traffic and mitochondrial localization. J. Cell Sci. 2014, 127, 1018–1032. [Google Scholar] [CrossRef] [PubMed] [Green Version]
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Rahman, K.U.; Yang, S.; Azam, N.; Yuan, Z.; Yu, J.; Zhao, C.; Feng, B. Mir-153-3p Modulates the Breast Cancer Cells’ Chemosensitivity to Doxorubicin by Targeting KIF20A. Cancers 2023, 15, 1724. https://doi.org/10.3390/cancers15061724
Rahman KU, Yang S, Azam N, Yuan Z, Yu J, Zhao C, Feng B. Mir-153-3p Modulates the Breast Cancer Cells’ Chemosensitivity to Doxorubicin by Targeting KIF20A. Cancers. 2023; 15(6):1724. https://doi.org/10.3390/cancers15061724
Chicago/Turabian StyleRahman, Khalil Ur, Shuo Yang, Nasir Azam, Zhen Yuan, Jiawen Yu, Chunhui Zhao, and Bin Feng. 2023. "Mir-153-3p Modulates the Breast Cancer Cells’ Chemosensitivity to Doxorubicin by Targeting KIF20A" Cancers 15, no. 6: 1724. https://doi.org/10.3390/cancers15061724