Exploring non-coding RNAs in Prostate Cancer: from Biomarkers to Therapeutic Strategies
Abstract
Prostate cancer (PCa) is the second most prevalent malignancy and a leading cause of cancer-related mortality in males worldwide. Despite advancements in therapeutic strategies, such as radical prostatectomy, radiotherapy, androgen deprivation therapy (ADT), and chemotherapy, treatment outcomes for metastatic castration-resistant PCa (mCRPC) remain suboptimal. The androgen receptor (AR) and its downstream signaling pathways play a critical role in PCa progression, with genetic aberrations, including AR amplification, TP53 and PTEN deletions, and MYC oncogene activation contributing to disease advancement. Although prostate-specific antigen (PSA)-based screening is widely used, its limitations in improving survival rates highlight the urgent need for more reliable biomarkers. Emerging evidence indicates that non-coding RNAs (ncRNAs), including long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and microRNAs (miRNAs), act as key regulators of gene expression, influencing PCa cell proliferation, apoptosis, invasion, and metastasis. Their differential expression across various stages of PCa underscores their potential as prognostic and diagnostic biomarkers as well as therapeutic targets. This review summarizes recent advancements in ncRNA research in PCa, providing insights into their mechanistic roles, clinical applications, and future directions in precision oncology
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13. Yan H, Bu P. Non-coding RNA in cancer. Essays Biochem. 2021;65(4):625–39. doi:10.1042/EBC20200032.
14. Kansara S, Pandey V, Lobie PE, Sethi G, Garg M, Pandey AK. Mechanistic involvement of long non-coding RNAs in onco-therapeutic resistance in triple-negative breast cancer. Cells. 2020;9(6):1511.
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24. Li Y, Luo H, Xiao N, Duan J, Wang Z, Wang S. Long noncoding RNA SChLAP1 accelerates proliferation and metastasis of prostate cancer via targeting miR-198 and promoting the MAPK1 pathway. Oncol Res. 2017;25(9):1607–17.
25. Huang X, Chen S, Wu C, Urabe F, et al. SChLAP1 regulates the metastasis and apoptosis of prostate cancer partly via miR-101. Transl Androl Urol. 2025 Jun 30;14(6):1782-1796. doi: 10.21037/tau-2025-316.
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27. Bhaskaran M, Mohan M. MicroRNAs: history, biogenesis, and their evolving role in animal development and disease. Vet Pathol. 2014;51(4):759–74.
28. Ghamlouche F, Yehya A, Zeid Y, Fakhereddine H, Fawaz J, Liu YN, et al. MicroRNAs as clinical tools for diagnosis, prognosis, and therapy in prostate cancer. Transl Oncol. 2023;28:101613.
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31. Metcalf GA. MicroRNAs: circulating biomarkers for the early detection of imperceptible cancers via biosensor and machine-learning advances. Oncogene. 2024;43(7):1–8. doi:10.1038/s41388-024-03076-3.
32. Garcia-Peterson LM, Li X. Trending topics of SIRT1 in tumorigenicity. Biochim Biophys Acta Gen Subj. 2021;1865(9):129952. doi:10.1016/j.bbagen.2021.129952.
33. Yang X, Yang Y, Gan R, Zhao L, Li W, Zhou H, et al. Down-regulation of miR-221 and miR-222 restrains prostate cancer cell proliferation and migration partly by activation of SIRT1. PLoS One. 2014;9(6):e98833.
34. Hossain A, Yamamura A, Nayeem MJ, Karnan S, et al. Rho kinase 2 promotes epithelial-mesenchymal transition and proliferation in human prostate cancer PC-3 cells. J Pharmacol Sci. 2025;159:229–41. doi:10.1016/j.jphs.2025.09.007.
35. Faramin Lashkarian, M., Hashemipour, N., Niaraki, N. et al. MicroRNA-122 in human cancers: from mechanistic to clinical perspectives. Cancer Cell Int 23, 29 (2023). https://doi.org/10.1186/s12935-023-02868-z
36. Zhu Z, Tang G, Yan J. MicroRNA-122 regulates docetaxel resistance of prostate cancer cells by regulating PKM2. Exp Ther Med. 2020;20(6):247. doi:10.3892/etm.2020.9377.
37. Chen LL, Yang L. Regulation of circRNA biogenesis. RNA Biol. 2015;12:381–8.
38. Liu X, Tong Y, Xia D, Peng E, Yang X, Liu H, et al. Circular RNAs in prostate cancer: biogenesis, biological functions, and clinical significance. Mol Ther Nucleic Acids. 2021;26:1130–47.
39. Pisignano G, Michael DC, Visal TH, Pirlog R, Ladomery M, Calin GA. Going circular: history, present, and future of circRNAs in cancer. Oncogene. 2023;42(38):2783–800.
40. Wei J, Li M, Xue C, Chen S, Zheng L, Deng H, et al. Understanding the roles and regulation patterns of circRNA on its host gene in tumorigenesis and tumor progression. J Exp Clin Cancer Res. 2023;42(1):86.
41. Xiao MS, Ai Y, Wilusz JE. Biogenesis and functions of circular RNAs come into focus. Trends Cell Biol. 2020;30:226–40.
42. Vo JN, Cieslik M, Zhang Y, Shukla S, Xiao L, Zhang Y, et al. The landscape of circular RNA in cancer. Cell. 2019;176:869–81.e13.
43. Jahani S, Nazeri E, Majidzadeh AK, Jahani M, Esmaeili R. Circular RNA: a new biomarker for breast cancer. J Cell Physiol. 2020;235:5501–10.
44. Wu G, Sun Y, Xiang Z, Wang K, Liu B, Xiao G, et al. Preclinical study using circular RNA 17 and microRNA-181c-5p to suppress enzalutamide-resistant prostate cancer progression. Cell Death Dis. 2019;10:37.
45. Rajappa A, Banerjee S, Sharma V, Khandelia P. Circular RNAs: emerging role in cancer diagnostics and therapeutics. Front Mol Biosci. 2020;7:577938.
46. Habrowska-Górczyńska DE, Kozieł MJ, Kowalska K, Piastowska-Ciesielska AW. FOXO3a and Its Regulators in Prostate Cancer. Int J Mol Sci. 2021 Nov 20;22(22):12530. doi: 10.3390/ijms222212530.
47. Shen Z, Zhou L, Zhang C, Xu J. Reduction of circular RNA Foxo3 promotes prostate cancer progression and chemoresistance to docetaxel. Cancer Lett. 2020;468:88–101.
48. Guan C, Zhang L, Wang S, et al. Upregulation of microRNA-21 promotes tumorigenesis of prostate cancer cells by targeting KLF5. Cancer Biol Ther. 2019;20(8):1149–61.
49. Nan C, Wang Y, Yang S, Chen Y. circCRKL suppresses progression of prostate cancer cells by regulating the miR-141/KLF5 axis. Pathol Res Pract. 2020;216(11):153182.
50. Mao Y, Li W, Hua B, Gu X, Pan W, Chen Q, et al. Circular RNA_PDHX promotes proliferation and invasion of prostate cancer by sponging miR-378a-3p. Front Cell Dev Biol. 2020;8:602707.
51. Wang JH, Wu XJ, Duan YZ, Li F. Circular RNA_CNST promotes tumorigenesis of osteosarcoma cells by sponging miR-421. Cell Transplant. 2020;29:963689720926147.
52. Chen J, Xie Q, Miao W, Fan J, Zhou X, Li M. CircPDHX promotes prostate cancer progression via the miR-497-5p/ACSL1 axis. Biochem Biophys Res Commun. 2022;620:35–41.
53. Qian Y, Shi L, Luo Z. Long non-coding RNAs in cancer: implications for diagnosis, prognosis, and therapy. Front Med. 2020;7:612393.
54. Dhanabalan D, Shanmugam N. Nanomedicine in cancer treatment – an overview. Adv Nat Sci Nanosci Nanotechnol. 2024;16(1):013001. doi:10.1088/2043-6254/ad72b9.
2. An C, Wang I, Li X, Xia R, Deng F. Long non-coding RNA in prostate cancer. Am J Clin Exp Urol. 2022;10(3):170–9.
3. Knipper S, Ott S, Schlemmer HP, Grimm MO, Graefen M, Wiegel T. Options for curative treatment of localized prostate cancer. Dtsch Arztebl Int. 2021;118:228–36. doi:10.3238/arztebl.m2021.0026.
4. Rebello RJ, Oing C, Knudsen KE, Loeb S, Johnson DC, Reiter RE, et al. Prostate cancer. Nat Rev Dis Primers. 2021;7(1):9.
5. Torre LA, Siegel RL, Ward EM, Jemal A. Global cancer incidence and mortality rates and trends—an update. Cancer Epidemiol Biomarkers Prev. 2016;25(1):16–27.
6. Ferri C, Di Biase A, Bocchetti M, Zappavigna S, Wagner S, Le Vu P, et al. miR-423-5p prevents MALAT1-mediated proliferation and metastasis in prostate cancer. J Exp Clin Cancer Res. 2022;41(1):20. doi:10.1186/s13046-021-02233-w.
7. He P, Xiong G, Guo W, Jiang G, Li Y, Li H. Long non-coding RNA CCAT2 promotes prostate cancer cell proliferation and invasion by regulating the Wnt/β-catenin signaling pathway. Oncol Lett. 2020;20(4):97. doi:10.3892/ol.2020.11958.
8. Wang Q, Feng J, Tang L. Non-coding RNA related to MAPK signaling pathway in liver cancer. Int J Mol Sci. 2022;23(19):11908. doi:10.3390/ijms231911908.
9. Diamantopoulos MA, Tsiakanikas P, Scorilas A. Non-coding RNAs: the riddle of the transcriptome and their perspectives in cancer. Ann Transl Med. 2018;6(12):241. doi:10.21037/atm.2018.06.10.
10. Slack FJ, Chinnaiyan AM. The role of non-coding RNAs in oncology. Cell. 2019;179(5):1033–55. doi:10.1016/j.cell.2019.10.017.
11. Uppaluri KR, Challa HJ, et al. Unlocking the potential of non-coding RNAs in cancer research and therapy. Transl Oncol. 2023;35:101730.
12. Li Y. Non-Coding RNA Performs Its Biological Function by Interacting with Macromolecules. Int J Mol Sci. 2023 Nov 13;24(22):16246. doi: 10.3390/ijms242216246.
13. Yan H, Bu P. Non-coding RNA in cancer. Essays Biochem. 2021;65(4):625–39. doi:10.1042/EBC20200032.
14. Kansara S, Pandey V, Lobie PE, Sethi G, Garg M, Pandey AK. Mechanistic involvement of long non-coding RNAs in onco-therapeutic resistance in triple-negative breast cancer. Cells. 2020;9(6):1511.
15. Mattick, J.S., Amaral, P.P., Carninci, P. et al. Long non-coding RNAs: definitions, functions, challenges and recommendations. Nat Rev Mol Cell Biol 24, 430–447 (2023). https://doi.org/10.1038/s41580-022-00566-8.
16. Janaththani P, Srinivasan SL, Batra J. Long non-coding RNAs at the chromosomal risk loci identified by prostate and breast cancer GWAS. Genes (Basel). 2021;12(12):2028. doi:10.3390/genes12122028.
17. Li P, Ma X, Gu X. The essential roles of lncRNAs/PI3K/AKT axis in gastrointestinal tumors. Front Cell Dev Biol. 2024;12:1442193. doi:10.3389/fcell.2024.1442193.
18. Rahbar Farzam O, Najafi S, Amini M, Rahimi Z, Dabbaghipour R, Zohdi O, et al. Interplay of miRNAs and lncRNAs in STAT3 signaling pathway in colorectal cancer progression. Cancer Cell Int. 2024;24(1):16. doi:10.1186/s12935-023-03202-3.
19. Lemos AEG, Matos ADR, Ferreira LB, Gimba ERP. The long non-coding RNA PCA3: an update of its functions and clinical applications as a biomarker in prostate cancer. Oncotarget. 2019 Nov 12;10(61):6589-6603. doi: 10.18632/oncotarget.27284.
20. Salameh A, Lee AK, Cardo-Vila M, Nunes DN, Efstathiou E, Staquicini FI, et al. PRUNE2 is a human prostate cancer suppressor regulated by the intronic long noncoding RNA PCA3. Proc Natl Acad Sci U S A. 2015;112(27):8403–8. doi:10.1073/pnas.1507882112.
21. Jiao Y, Xu Y, Liu C, Miao R, Liu C, Wang Y, et al. The role of ADAR1 through and beyond its editing activity in cancer. Cell Commun Signal. 2024;22(1):42. doi:10.1186/s12964-023-01465-x.
22. Lemos A, Goulart E, Matos A, Rocha M, Ferreira L, Bueno B, Gimba E. The long non-coding RNA PCA3: an update of its functions and clinical applications as a biomarker in prostate cancer. Oncotarget. 2019;10:6589–603.
23. Huang X, Chen S, Wu C, et al. SChLAP1 regulates the metastasis and apoptosis of prostate cancer partly via miR-101. Transl Androl Urol. 2025; 14(6): doi: 10.21037/tau-2025-316
24. Li Y, Luo H, Xiao N, Duan J, Wang Z, Wang S. Long noncoding RNA SChLAP1 accelerates proliferation and metastasis of prostate cancer via targeting miR-198 and promoting the MAPK1 pathway. Oncol Res. 2017;25(9):1607–17.
25. Huang X, Chen S, Wu C, Urabe F, et al. SChLAP1 regulates the metastasis and apoptosis of prostate cancer partly via miR-101. Transl Androl Urol. 2025 Jun 30;14(6):1782-1796. doi: 10.21037/tau-2025-316.
26. Rzeszutek I, Singh A. Small RNAs, big diseases. Int J Mol Sci. 2020;21(16):5699. doi:10.3390/ijms21165699.
27. Bhaskaran M, Mohan M. MicroRNAs: history, biogenesis, and their evolving role in animal development and disease. Vet Pathol. 2014;51(4):759–74.
28. Ghamlouche F, Yehya A, Zeid Y, Fakhereddine H, Fawaz J, Liu YN, et al. MicroRNAs as clinical tools for diagnosis, prognosis, and therapy in prostate cancer. Transl Oncol. 2023;28:101613.
29. Jiao X, Qian X, Wu L, Li B, Wang Y, Kong X, et al. MicroRNA: the impact on cancer stemness and therapeutic resistance. Cells. 2019;9(1):8. doi:10.3390/cells9010008.
30. Syeda ZA, Langden SSS, Munkhzul C, Lee M, Song SJ. Regulatory mechanism of microRNA expression in cancer. Int J Mol Sci. 2020;21(5):1723. doi:10.3390/ijms21051723.
31. Metcalf GA. MicroRNAs: circulating biomarkers for the early detection of imperceptible cancers via biosensor and machine-learning advances. Oncogene. 2024;43(7):1–8. doi:10.1038/s41388-024-03076-3.
32. Garcia-Peterson LM, Li X. Trending topics of SIRT1 in tumorigenicity. Biochim Biophys Acta Gen Subj. 2021;1865(9):129952. doi:10.1016/j.bbagen.2021.129952.
33. Yang X, Yang Y, Gan R, Zhao L, Li W, Zhou H, et al. Down-regulation of miR-221 and miR-222 restrains prostate cancer cell proliferation and migration partly by activation of SIRT1. PLoS One. 2014;9(6):e98833.
34. Hossain A, Yamamura A, Nayeem MJ, Karnan S, et al. Rho kinase 2 promotes epithelial-mesenchymal transition and proliferation in human prostate cancer PC-3 cells. J Pharmacol Sci. 2025;159:229–41. doi:10.1016/j.jphs.2025.09.007.
35. Faramin Lashkarian, M., Hashemipour, N., Niaraki, N. et al. MicroRNA-122 in human cancers: from mechanistic to clinical perspectives. Cancer Cell Int 23, 29 (2023). https://doi.org/10.1186/s12935-023-02868-z
36. Zhu Z, Tang G, Yan J. MicroRNA-122 regulates docetaxel resistance of prostate cancer cells by regulating PKM2. Exp Ther Med. 2020;20(6):247. doi:10.3892/etm.2020.9377.
37. Chen LL, Yang L. Regulation of circRNA biogenesis. RNA Biol. 2015;12:381–8.
38. Liu X, Tong Y, Xia D, Peng E, Yang X, Liu H, et al. Circular RNAs in prostate cancer: biogenesis, biological functions, and clinical significance. Mol Ther Nucleic Acids. 2021;26:1130–47.
39. Pisignano G, Michael DC, Visal TH, Pirlog R, Ladomery M, Calin GA. Going circular: history, present, and future of circRNAs in cancer. Oncogene. 2023;42(38):2783–800.
40. Wei J, Li M, Xue C, Chen S, Zheng L, Deng H, et al. Understanding the roles and regulation patterns of circRNA on its host gene in tumorigenesis and tumor progression. J Exp Clin Cancer Res. 2023;42(1):86.
41. Xiao MS, Ai Y, Wilusz JE. Biogenesis and functions of circular RNAs come into focus. Trends Cell Biol. 2020;30:226–40.
42. Vo JN, Cieslik M, Zhang Y, Shukla S, Xiao L, Zhang Y, et al. The landscape of circular RNA in cancer. Cell. 2019;176:869–81.e13.
43. Jahani S, Nazeri E, Majidzadeh AK, Jahani M, Esmaeili R. Circular RNA: a new biomarker for breast cancer. J Cell Physiol. 2020;235:5501–10.
44. Wu G, Sun Y, Xiang Z, Wang K, Liu B, Xiao G, et al. Preclinical study using circular RNA 17 and microRNA-181c-5p to suppress enzalutamide-resistant prostate cancer progression. Cell Death Dis. 2019;10:37.
45. Rajappa A, Banerjee S, Sharma V, Khandelia P. Circular RNAs: emerging role in cancer diagnostics and therapeutics. Front Mol Biosci. 2020;7:577938.
46. Habrowska-Górczyńska DE, Kozieł MJ, Kowalska K, Piastowska-Ciesielska AW. FOXO3a and Its Regulators in Prostate Cancer. Int J Mol Sci. 2021 Nov 20;22(22):12530. doi: 10.3390/ijms222212530.
47. Shen Z, Zhou L, Zhang C, Xu J. Reduction of circular RNA Foxo3 promotes prostate cancer progression and chemoresistance to docetaxel. Cancer Lett. 2020;468:88–101.
48. Guan C, Zhang L, Wang S, et al. Upregulation of microRNA-21 promotes tumorigenesis of prostate cancer cells by targeting KLF5. Cancer Biol Ther. 2019;20(8):1149–61.
49. Nan C, Wang Y, Yang S, Chen Y. circCRKL suppresses progression of prostate cancer cells by regulating the miR-141/KLF5 axis. Pathol Res Pract. 2020;216(11):153182.
50. Mao Y, Li W, Hua B, Gu X, Pan W, Chen Q, et al. Circular RNA_PDHX promotes proliferation and invasion of prostate cancer by sponging miR-378a-3p. Front Cell Dev Biol. 2020;8:602707.
51. Wang JH, Wu XJ, Duan YZ, Li F. Circular RNA_CNST promotes tumorigenesis of osteosarcoma cells by sponging miR-421. Cell Transplant. 2020;29:963689720926147.
52. Chen J, Xie Q, Miao W, Fan J, Zhou X, Li M. CircPDHX promotes prostate cancer progression via the miR-497-5p/ACSL1 axis. Biochem Biophys Res Commun. 2022;620:35–41.
53. Qian Y, Shi L, Luo Z. Long non-coding RNAs in cancer: implications for diagnosis, prognosis, and therapy. Front Med. 2020;7:612393.
54. Dhanabalan D, Shanmugam N. Nanomedicine in cancer treatment – an overview. Adv Nat Sci Nanosci Nanotechnol. 2024;16(1):013001. doi:10.1088/2043-6254/ad72b9.
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| Issue | Vol 17 No 2 (2025) | |
| Section | Reviews | |
| Keywords | ||
| Prostate cancer non-coding RNAs long non-coding RNAs Circular RNAs MicroRNAs Therapeutic targets. | ||
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How to Cite
1.
Dhanabalan D, Shanmugam N. Exploring non-coding RNAs in Prostate Cancer: from Biomarkers to Therapeutic Strategies. Basic Clin Cancer Res. 2026;17(2):241-251.
