Developing Folate-Conjugated miR-34a Therapeutic for Prostate Cancer: Challenges and Promises
Abstract
:1. Introduction
2. Results
2.1. miR-34a Expression Is Downregulated in PCa That Has TP53 Loss or Mutations
2.2. miR-34a Mimic Downregulated miR-34a Targets and Inhibited PCa Cell Growth
2.3. Folate–miR-34a Inhibited the Growth of Breast, Ovarian, and Cervical but Not PCa Cells
2.4. Lack of FOLR1 Expression in PCa
2.5. Folate–miR-34a Also Did Not Accumulate Nor Show Any Effect in PSMA-Expressing PCa Cells
3. Discussion
4. Materials and Methods
4.1. Cell Lines and Animals
4.2. Preparation of Folate–miR-34a Duplex
4.3. RNA Isolation and Real-Time RT-PCR Analysis
4.4. In Vitro Renilla Luciferase Assay
4.5. Cell Proliferation Assays
4.6. Western Blotting
4.7. Immunofluorescence (IF)
4.8. Flow Cytometry
4.9. Fluorescence Microscopy
4.10. Whole Body Imaging and Tissue Biodistribution
4.11. Statistical Analysis
5. Conclusions
- Folate–miR-34a did not elicit PCa-inhibitory effects due to a lack of appreciable expression of FOLR1 in PCa cells.
- Folate–miR-34a also did not display any apparent effect on PCa cells expressing PMSA despite folate’s reported binding capability to PSMA.
- Folate–miR-34a exhibited impressive inhibitory effects on breast, ovarian, and cervical cancer cells that do express FOLR1, suggesting its potential therapeutic application on FOLR1-expressing cancers.
- The insights offered by the current study highlight challenges in the specific delivery of folate–miR-34a to PCa due to the lack of target receptor expression and shed light on the future development of ligand-conjugated miR-34a as potential therapeutics for advanced and aggressive PCa.
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Sartor, O.; de Bono, J.S. Metastatic Prostate Cancer. N. Engl. J. Med. 2018, 378, 645–657. [Google Scholar] [CrossRef]
- Rice, M.A.; Malhotra, S.V.; Stoyanova, T. Second-Generation Antiandrogens: From Discovery to Standard of Care in Castration Resistant Prostate Cancer. Front. Oncol. 2019, 9, 801. [Google Scholar] [CrossRef]
- Qin, J.; Liu, X.; Laffin, B.; Chen, X.; Choy, G.; Jeter, C.R.; Calhoun-Davis, T.; Li, H.; Palapattu, G.S.; Pang, S.; et al. The PSA(-/lo) prostate cancer cell population harbors self-renewing long-term tumor-propagating cells that resist castration. Cell Stem Cell 2012, 10, 556–569. [Google Scholar] [CrossRef]
- Li, Q.; Deng, Q.; Chao, H.-P.; Liu, X.; Lu, Y.; Lin, K.; Liu, B.; Tang, G.W.; Zhang, D.; Tracz, A.; et al. Linking prostate cancer cell AR heterogeneity to distinct castration and enzalutamide responses. Nat. Commun. 2018, 9, 3600. [Google Scholar] [CrossRef] [PubMed]
- Li, W.J.; Liu, X.; Dougherty, E.M.; Tang, D.G. MicroRNA-34a, Prostate Cancer Stem Cells, and Therapeutic Development. Cancers 2022, 14, 4538. [Google Scholar] [CrossRef] [PubMed]
- Liu, X.; Li, W.; Puzanov, I.; Goodrich, D.W.; Chatta, G.; Tang, D.G. Prostate cancer as a dedifferentiated organ: Androgen receptor, cancer stem cells, and cancer stemness. Essays Biochem. 2022, 66, 291–303. [Google Scholar] [CrossRef] [PubMed]
- 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] [PubMed]
- Zhang, L.; Liao, Y.; Tang, L. MicroRNA-34 family: A potential tumor suppressor and therapeutic candidate in cancer. J. Exp. Clin. Cancer Res. 2019, 38, 53. [Google Scholar] [CrossRef]
- Zhang, G.; Tian, X.; Li, Y.; Wang, Z.; Li, X.; Zhu, C. miR-27b and miR-34a enhance docetaxel sensitivity of prostate cancer cells through inhibiting epithelial-to-mesenchymal transition by targeting ZEB1. Biomed. Pharmacother. 2018, 97, 736–744. [Google Scholar] [CrossRef]
- Gaur, S.; Wen, Y.; Song, J.H.; Parikh, N.U.; Mangala, L.S.; Blessing, A.M.; Ivan, C.; Wu, S.Y.; Varkaris, A.; Shi, Y.; et al. Chitosan nanoparticle-mediated delivery of miRNA-34a decreases prostate tumor growth in the bone and its expression induces non-canonical autophagy. Oncotarget 2015, 6, 29161–29177. [Google Scholar] [CrossRef]
- Liu, C.; Kelnar, K.; Liu, B.; Chen, X.; Calhoun-Davis, T.; Li, H.; Patrawala, L.; Yan, H.; Jeter, C.; Honorio, S.; et al. The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44. Nat. Med. 2011, 17, 211–215. [Google Scholar] [CrossRef]
- Yamamura, S.; Saini, S.; Majid, S.; Hirata, H.; Ueno, K.; Deng, G.; Dahiya, R. MicroRNA-34a modulates c-Myc transcriptional complexes to suppress malignancy in human prostate cancer cells. PLoS ONE 2012, 7, e29722. [Google Scholar] [CrossRef] [PubMed]
- Chen, W.Y.; Liu, S.Y.; Chang, Y.S.; Yin, J.J.; Yeh, H.L.; Mouhieddine, T.H.; Hadadeh, O.; Abou-Kheir, W.; Liu, Y.N. MicroRNA-34a regulates WNT/TCF7 signaling and inhibits bone metastasis in Ras-activated prostate cancer. Oncotarget 2015, 6, 441–457. [Google Scholar] [CrossRef] [PubMed]
- Alves-Fernandes, D.K.; Jasiulionis, M.G. The Role of SIRT1 on DNA Damage Response and Epigenetic Alterations in Cancer. Int. J. Mol. Sci. 2019, 20, 3153. [Google Scholar] [CrossRef] [PubMed]
- Kojima, K.; Fujita, Y.; Nozawa, Y.; Deguchi, T.; Ito, M. MiR-34a attenuates paclitaxel-resistance of hormone-refractory prostate cancer PC3 cells through direct and indirect mechanisms. Prostate 2010, 70, 1501–1512. [Google Scholar] [CrossRef] [PubMed]
- Corcoran, C.; Rani, S.; O’Driscoll, L. miR-34a is an intracellular and exosomal predictive biomarker for response to docetaxel with clinical relevance to prostate cancer progression. Prostate 2014, 74, 1320–1334. [Google Scholar] [CrossRef] [PubMed]
- Dowdy, S.F. Overcoming cellular barriers for RNA therapeutics. Nat. Biotechnol. 2017, 35, 222–229. [Google Scholar] [CrossRef] [PubMed]
- Segal, M.; Slack, F.J. Challenges identifying efficacious miRNA therapeutics for cancer. Expert. Opin. Drug. Discov. 2020, 15, 987–992. [Google Scholar] [CrossRef] [PubMed]
- Abdelaal, A.M.; Kasinski, A.L. Ligand-mediated delivery of RNAi-based therapeutics for the treatment of oncological diseases. NAR Cancer 2021, 3, zcab030. [Google Scholar] [CrossRef]
- Chen, Y.; Gao, D.Y.; Huang, L. In vivo delivery of miRNAs for cancer therapy: Challenges and strategies. Adv. Drug Deliv. Rev. 2015, 81, 128–141. [Google Scholar] [CrossRef]
- Orellana, E.A.; Tenneti, S.; Rangasamy, L.; Lyle, L.T.; Low, P.S.; Kasinski, A.L. FolamiRs: Ligand-targeted, vehicle-free delivery of microRNAs for the treatment of cancer. Sci. Transl. Med. 2017, 9, eaam9327. [Google Scholar] [CrossRef] [PubMed]
- Leamon, C.P.; Low, P.S. Folate-mediated targeting: From diagnostics to drug and gene delivery. Drug Discov. Today 2001, 6, 44–51. [Google Scholar] [CrossRef]
- Kularatne, S.A.; Wang, K.; Santhapuram, H.K.R.; Low, P.S. Prostate-Specific Membrane Antigen Targeted Imaging and Therapy of Prostate Cancer Using a PSMA Inhibitor as a Homing Ligand. Mol. Pharm. 2009, 6, 780–789. [Google Scholar] [CrossRef]
- Bravaccini, S.; Puccetti, M.; Bocchini, M.; Ravaioli, S.; Celli, M.; Scarpi, E.; De Giorgi, U.; Tumedei, M.M.; Raulli, G.; Cardinale, L.; et al. PSMA expression: A potential ally for the pathologist in prostate cancer diagnosis. Sci. Rep. 2018, 8, 4254. [Google Scholar] [CrossRef]
- Sheehan, B.; Guo, C.; Neeb, A.; Paschalis, A.; Sandhu, S.; de Bono, J.S. Prostate-specific Membrane Antigen Biology in Lethal Prostate Cancer and its Therapeutic Implications. Eur. Urol. Focus 2021, 8, 1157–1168. [Google Scholar] [CrossRef]
- Wang, F.; Li, Z.; Feng, X.; Yang, D.; Lin, M. Advances in PSMA-targeted therapy for prostate cancer. Prostate Cancer Prostatic Dis. 2022, 25, 11–26. [Google Scholar] [CrossRef] [PubMed]
- He, L.; He, X.; Lim, L.P.; de Stanchina, E.; Xuan, Z.; Liang, Y.; Xue, W.; Zender, L.; Magnus, J.; Ridzon, D.; et al. A microRNA component of the p53 tumour suppressor network. Nature 2007, 447, 1130–1134. [Google Scholar] [CrossRef] [PubMed]
- Chang, T.C.; Wentzel, E.A.; Kent, O.A.; Ramachandran, K.; Mullendore, M.; Lee, K.H.; Feldmann, G.; Yamakuchi, M.; Ferlito, M.; Lowenstein, C.J.; et al. Transactivation of miR-34a by p53 broadly influences gene expression and promotes apoptosis. Mol. Cell 2007, 26, 745–752. [Google Scholar] [CrossRef]
- Raver-Shapira, N.; Marciano, E.; Meiri, E.; Spector, Y.; Rosenfeld, N.; Moskovits, N.; Bentwich, Z.; Oren, M. Transcriptional activation of miR-34a contributes to p53-mediated apoptosis. Mol. Cell 2007, 26, 731–743. [Google Scholar] [CrossRef]
- Zhang, D.; Park, D.; Zhong, Y.; Lu, Y.; Rycaj, K.; Gong, S.; Chen, X.; Liu, X.; Chao, H.P.; Whitney, P.; et al. Stem cell and neurogenic gene-expression profiles link prostate basal cells to aggressive prostate cancer. Nat. Commun. 2016, 7, 10798. [Google Scholar] [CrossRef]
- Rajan, P.; Sudbery, I.M.; Villasevil, M.E.; Mui, E.; Fleming, J.; Davis, M.; Ahmad, I.; Edwards, J.; Sansom, O.J.; Sims, D.; et al. Next-generation sequencing of advanced prostate cancer treated with androgen-deprivation therapy. Eur. Urol. 2014, 66, 32–39. [Google Scholar] [CrossRef]
- Sharma, N.V.; Pellegrini, K.L.; Ouellet, V.; Giuste, F.O.; Ramalingam, S.; Watanabe, K.; Adam-Granger, E.; Fossouo, L.; You, S.; Freeman, M.R.; et al. Identification of the Transcription Factor Relationships Associated with Androgen Deprivation Therapy Response and Metastatic Progression in Prostate Cancer. Cancers 2018, 10, 379. [Google Scholar] [CrossRef]
- Jeitner, T.M.; Babich, J.W.; Kelly, J.M. Advances in PSMA theranostics. Transl. Oncol. 2022, 22, 101450. [Google Scholar] [CrossRef]
- Yao, V.; Berkman, C.E.; Choi, J.K.; O’Keefe, D.S.; Bacich, D.J. Expression of prostate-specific membrane antigen (PSMA), increases cell folate uptake and proliferation and suggests a novel role for PSMA in the uptake of the non-polyglutamated folate, folic acid. Prostate 2010, 70, 305–316. [Google Scholar] [CrossRef]
- Maurer, T.; Eiber, M.; Schwaiger, M.; Gschwend, J.E. Current use of PSMA-PET in prostate cancer management. Nat. Rev. Urol. 2016, 13, 226–235. [Google Scholar] [CrossRef]
- Liu, H.; Rajasekaran, A.K.; Moy, P.; Xia, Y.; Kim, S.; Navarro, V.; Rahmati, R.; Bander, N.H. Constitutive and antibody-induced internalization of prostate-specific membrane antigen. Cancer Res. 1998, 58, 4055–4060. [Google Scholar]
- Ghosh, A.; Heston, W.D. Tumor target prostate specific membrane antigen (PSMA) and its regulation in prostate cancer. J. Cell Biochem. 2004, 91, 528–539. [Google Scholar] [CrossRef]
- Flores, O.; Santra, S.; Kaittanis, C.; Bassiouni, R.; Khaled, A.S.; Khaled, A.R.; Grimm, J.; Perez, J.M. PSMA-Targeted Theranostic Nanocarrier for Prostate Cancer. Theranostics 2017, 7, 2477–2494. [Google Scholar] [CrossRef] [PubMed]
- Beg, M.S.; Brenner, A.J.; Sachdev, J.; Borad, M.; Kang, Y.-K.; Stoudemire, J.; Smith, S.; Bader, A.G.; Kim, S.; Hong, D.S. Phase I study of MRX34, a liposomal miR-34a mimic, administered twice weekly in patients with advanced solid tumors. Investig. New Drugs 2017, 35, 180–188. [Google Scholar] [CrossRef] [PubMed]
- Hong, D.S.; Kang, Y.-K.; Borad, M.; Sachdev, J.; Ejadi, S.; Lim, H.Y.; Brenner, A.J.; Park, K.; Lee, J.-L.; Kim, T.-Y.; et al. Phase 1 study of MRX34, a liposomal miR-34a mimic, in patients with advanced solid tumours. Br. J. Cancer 2020, 122, 1630–1637. [Google Scholar] [CrossRef] [PubMed]
- Rajasekaran, A.K.; Anilkumar, G.; Christiansen, J.J. Is prostate-specific membrane antigen a multifunctional protein? Am. J. Physiol. Cell Physiol. 2005, 288, C975–C981. [Google Scholar] [CrossRef]
- Evans, J.C.; Malhotra, M.; Guo, J.; O’Shea, J.P.; Hanrahan, K.; O’Neill, A.; Landry, W.D.; Griffin, B.T.; Darcy, R.; Watson, R.W.; et al. Folate-targeted amphiphilic cyclodextrin.siRNA nanoparticles for prostate cancer therapy exhibit PSMA mediated uptake, therapeutic gene silencing in vitro and prolonged circulation in vivo. Nanomedicine 2016, 12, 2341–2351. [Google Scholar] [CrossRef]
- Jivrajani, M.; Nivsarkar, M. Ligand-targeted bacterial minicells: Futuristic nano-sized drug delivery system for the efficient and cost effective delivery of shRNA to cancer cells. Nanomedicine 2016, 12, 2485–2498. [Google Scholar] [CrossRef]
- Patil, Y.; Shmeeda, H.; Amitay, Y.; Ohana, P.; Kumar, S.; Gabizon, A. Targeting of folate-conjugated liposomes with co-entrapped drugs to prostate cancer cells via prostate-specific membrane antigen (PSMA). Nanomedicine 2018, 14, 1407–1416. [Google Scholar] [CrossRef] [PubMed]
- Xiang, B.; Dong, D.W.; Shi, N.Q.; Gao, W.; Yang, Z.Z.; Cui, Y.; Cao, D.Y.; Qi, X.R. PSA-responsive and PSMA-mediated multifunctional liposomes for targeted therapy of prostate cancer. Biomaterials 2013, 34, 6976–6991. [Google Scholar] [CrossRef] [PubMed]
- Chen, Y.L.; Chang, M.C.; Huang, C.Y.; Chiang, Y.C.; Lin, H.W.; Chen, C.A.; Hsieh, C.Y.; Cheng, W.F. Serous ovarian carcinoma patients with high alpha-folate receptor had reducing survival and cytotoxic chemo-response. Mol. Oncol. 2012, 6, 360–369. [Google Scholar] [CrossRef] [PubMed]
- Liu, C.; Ding, L.; Bai, L.; Chen, X.; Kang, H.; Hou, L.; Wang, J. Folate receptor alpha is associated with cervical carcinogenesis and regulates cervical cancer cells growth by activating ERK1/2/c-Fos/c-Jun. Biochem. Biophys. Res. Commun. 2017, 491, 1083–1091. [Google Scholar] [CrossRef] [PubMed]
- Scaranti, M.; Cojocaru, E.; Banerjee, S.; Banerji, U. Exploiting the folate receptor alpha in oncology. Nat. Rev. Clin. Oncol. 2020, 17, 349–359. [Google Scholar] [CrossRef] [PubMed]
- Zamarin, D.; Walderich, S.; Holland, A.; Zhou, Q.; Iasonos, A.E.; Torrisi, J.M.; Merghoub, T.; Chesebrough, L.F.; McDonnell, A.S.; Gallagher, J.M.; et al. Safety, immunogenicity, and clinical efficacy of durvalumab in combination with folate receptor alpha vaccine TPIV200 in patients with advanced ovarian cancer: A phase II trial. J. Immunother. Cancer 2020, 8, e000829. [Google Scholar] [CrossRef] [PubMed]
- Moore, K.N.; Oza, A.M.; Colombo, N.; Oaknin, A.; Scambia, G.; Lorusso, D.; Konecny, G.E.; Banerjee, S.; Murphy, C.G.; Tanyi, J.L.; et al. Phase III, randomized trial of mirvetuximab soravtansine versus chemotherapy in patients with platinum-resistant ovarian cancer: Primary analysis of FORWARD I. Ann. Oncol. 2021, 32, 757–765. [Google Scholar] [CrossRef]
- Kim, H.; Kim, M.W.; Jeong, Y.I.; Yang, H.S. Redox-Sensitive and Folate-Receptor-Mediated Targeting of Cervical Cancer Cells for Photodynamic Therapy Using Nanophotosensitizers Composed of Chlorin e6-Conjugated beta-Cyclodextrin via Diselenide Linkage. Cells 2021, 10, 2190. [Google Scholar] [CrossRef]
- McGray, A.J.R.; Chiello, J.L.; Tsuji, T.; Long, M.; Maraszek, K.; Gaulin, N.; Rosario, S.R.; Hess, S.M.; Abrams, S.I.; Kozbor, D.; et al. BiTE secretion by adoptively transferred stem-like T cells improves FRalpha+ ovarian cancer control. J. Immunother. Cancer 2023, 11, e006863. [Google Scholar] [CrossRef]
- Thomas, M.; Kularatne, S.A.; Qi, L.; Kleindl, P.; Leamon, C.P.; Hansen, M.J.; Low, P.S. Ligand-targeted delivery of small interfering RNAs to malignant cells and tissues. Ann. N. Y. Acad. Sci. 2009, 1175, 32–39. [Google Scholar] [CrossRef]
- Tai, W.; Li, J.; Corey, E.; Gao, X. A ribonucleoprotein octamer for targeted siRNA delivery. Nat. Biomed. Eng. 2018, 2, 326–337. [Google Scholar] [CrossRef]
- Pei, D.; Buyanova, M. Overcoming Endosomal Entrapment in Drug Delivery. Bioconjug. Chem. 2019, 30, 273–283. [Google Scholar] [CrossRef] [PubMed]
- Dowdy, S.F.; Setten, R.L.; Cui, X.S.; Jadhav, S.G. Delivery of RNA Therapeutics: The Great Endosomal Escape! Nucleic Acid Ther. 2022, 32, 361–368. [Google Scholar] [CrossRef] [PubMed]
- Gao, Y.; Li, Y.; Li, Y.; Yuan, L.; Zhou, Y.; Li, J.; Zhao, L.; Zhang, C.; Li, X.; Liu, Y. PSMA-mediated endosome escape-accelerating polymeric micelles for targeted therapy of prostate cancer and the real time tracing of their intracellular trafficking. Nanoscale 2015, 7, 597–612. [Google Scholar] [CrossRef] [PubMed]
- Caron, N.J.; Quenneville, S.P.; Tremblay, J.P. Endosome disruption enhances the functional nuclear delivery of Tat-fusion proteins. Biochem. Biophys. Res. Commun. 2004, 319, 12–20. [Google Scholar] [CrossRef] [PubMed]
- Chen, S.; Wang, S.; Kopytynski, M.; Bachelet, M.; Chen, R. Membrane-Anchoring, Comb-Like Pseudopeptides for Efficient, pH-Mediated Membrane Destabilization and Intracellular Delivery. ACS Appl. Mater. Interfaces 2017, 9, 8021–8029. [Google Scholar] [CrossRef]
- Hassler, M.R.; Turanov, A.A.; Alterman, J.F.; Haraszti, R.A.; Coles, A.H.; Osborn, M.F.; Echeverria, D.; Nikan, M.; Salomon, W.E.; Roux, L.; et al. Comparison of partially and fully chemically-modified siRNA in conjugate-mediated delivery in vivo. Nucleic Acids Res. 2018, 46, 2185–2196. [Google Scholar] [CrossRef] [PubMed]
- Abdelaal, A.M.; Sohal, I.S.; Iyer, S.; Sudarshan, K.; Kothandaraman, H.; Lanman, N.A.; Low, P.S.; Kasinski, A.L. A first-in-class fully modified version of miR-34a with outstanding stability, activity, and anti-tumor efficacy. Oncogene 2023, 42, 2985–2999. [Google Scholar] [CrossRef] [PubMed]
- Bakht, M.K.; Yamada, Y.; Ku, S.Y.; Venkadakrishnan, V.B.; Korsen, J.A.; Kalidindi, T.M.; Mizuno, K.; Ahn, S.H.; Seo, J.H.; Garcia, M.M.; et al. Landscape of prostate-specific membrane antigen heterogeneity and regulation in AR-positive and AR-negative metastatic prostate cancer. Nat. Cancer 2023, 4, 699–715. [Google Scholar] [CrossRef] [PubMed]
- Paschalis, A.; Sheehan, B.; Riisnaes, R.; Rodrigues, D.N.; Gurel, B.; Bertan, C.; Ferreira, A.; Lambros, M.B.K.; Seed, G.; Yuan, W.; et al. Prostate-specific Membrane Antigen Heterogeneity and DNA Repair Defects in Prostate Cancer. Eur. Urol. 2019, 76, 469–478. [Google Scholar] [CrossRef] [PubMed]
- Sayar, E.; Patel, R.A.; Coleman, I.M.; Roudier, M.P.; Zhang, A.; Mustafi, P.; Low, J.Y.; Hanratty, B.; Ang, L.S.; Bhatia, V.; et al. Reversible epigenetic alterations mediate PSMA expression heterogeneity in advanced metastatic prostate cancer. JCI Insight 2023, 8, e162907. [Google Scholar] [CrossRef]
- Sartor, O.; de Bono, J.; Chi, K.N.; Fizazi, K.; Herrmann, K.; Rahbar, K.; Tagawa, S.T.; Nordquist, L.T.; Vaishampayan, N.; El-Haddad, G.; et al. Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. N. Engl. J. Med. 2021, 385, 1091–1103. [Google Scholar] [CrossRef]
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. |
© 2024 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
Li, W.; Wang, Y.; Liu, X.; Wu, S.; Wang, M.; Turowski, S.G.; Spernyak, J.A.; Tracz, A.; Abdelaal, A.M.; Sudarshan, K.; et al. Developing Folate-Conjugated miR-34a Therapeutic for Prostate Cancer: Challenges and Promises. Int. J. Mol. Sci. 2024, 25, 2123. https://doi.org/10.3390/ijms25042123
Li W, Wang Y, Liu X, Wu S, Wang M, Turowski SG, Spernyak JA, Tracz A, Abdelaal AM, Sudarshan K, et al. Developing Folate-Conjugated miR-34a Therapeutic for Prostate Cancer: Challenges and Promises. International Journal of Molecular Sciences. 2024; 25(4):2123. https://doi.org/10.3390/ijms25042123
Chicago/Turabian StyleLi, Wen (Jess), Yunfei Wang, Xiaozhuo Liu, Shan Wu, Moyi Wang, Steven G. Turowski, Joseph A. Spernyak, Amanda Tracz, Ahmed M. Abdelaal, Kasireddy Sudarshan, and et al. 2024. "Developing Folate-Conjugated miR-34a Therapeutic for Prostate Cancer: Challenges and Promises" International Journal of Molecular Sciences 25, no. 4: 2123. https://doi.org/10.3390/ijms25042123