Diagnostic and Prognostic Value of miR-93 in Prostate Cancer: A Meta-Analysis and Bioinformatics Analysis
-
Hassane Gazzaz
,
Maha El Habchi
,
Mohammed El Feniche
,
Yassine El Aatik
,
Abdelghani El Ouardi
,
Ahmed Ameur
,
Abdellah Dami
Abstract
Background: Accurate and non-invasive diagnostic and prognostic markers are necessary to improve patient outcomes. MicroRNAs have been proposed as relatively non-invasive and pertinent biomarkers. miR-93 has been studied for its potential as a diagnostic and prognostic marker in prostate cancer (PCa), but findings from individual studies are inconsistent. We conducted a meta-analysis of its overall differential expression in 13 PCa studies and a bioinformatics analysis to provide a comprehensive appraisal of its diagnostic and prognostic role.
Methods: We searched all published papers on miR-93 expression in PCa up to Nov 30, 2022 using PubMed, Science Direct, Web of Science, Cochrane Central Register of Controlled Trials databases. We used RevMan software to Meta-analyze the included literature. A bioinformatics analysis of genes and pathways that might be target to the effect of the mature miR-93-5p was carried out.
Results: The pooled standardized mean difference (SMD) of miR-93 expression in PCa, its area under the curve (AUC) and hazard ratio (HR) were 1.26, 95% CI [-0.34–2.86], 0.84, 95% CI [0.76 –0.93] and 1.67, 95% CI [0.98, 2.84] respectively. Bioinformatics analysis revealed that mature miR-93-5p may regulate genes such as SMAD1, SMAD7 and MAPK and the PI3K-Akt signaling pathways.
Conclusion: miR-93 has significant diagnostic and prognostic value in PCa. These findings highlight the potential of miR-93 as a non-invasive biomarker for PCa and may contribute to earlier detection and prognostic assessment. The target genes and signaling pathways regulated by miR-93 may provide insights into the underlying molecular mechanisms of PCa.
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8. Cao Z, Guo Y, Ao Y, Zhou S (2020). Dysregulated microRNAs in laryngeal cancer: a comprehensive meta-analysis using a robust rank aggregation ap-proach. Future Oncol, 16(33):2723–34.
9. Mitchell PS, Parkin RK, Kroh EM, et al (2008). Circulating microRNAs as stable blood-based markers for cancer detec-tion. Proc Natl Acad Sci USA, 105(30):10513–8.
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11. Choi N, Park J, Lee JS, et al (2015). miR-93/miR-106b/miR-375-CIC-CRABP1: a novel regulatory axis in prostate cancer progression. Oncotarget, 6(27):23533–47.
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13. Liu JJ, Zhang X, Wu XH (2018). miR-93 Promotes the Growth and Invasion of Prostate Cancer by Upregulating Its Target Genes TGFBR2, ITGB8, and LATS2. Mol Ther Oncolytics, 11:14–9.
14. Yang K, Gao ZY, Li TQ, et al (2019). An-ti-tumor activity and the mechanism of a green tea (Camellia sinensis) polysac-charide on prostate cancer. Int J Biol Macromol, 122:95–103.
15. Zedan AH, Osther PJS, Assenholt J, Madsen JS, Hansen TF (2020). Circulat-ing miR-141 and miR-375 are associated with treatment outcome in metastatic castration resistant prostate cancer. Sci Rep, 10(1):227.
16. Martínez-González LJ, Sánchez-Conde V, González-Cabezuelo JM, et al (2021). Identification of MicroRNAs as Viable Aggressiveness Biomarkers for Prostate Cancer. Biomedicines, 9(6):646.
17. Zhang S, Liu C, Zou X, et al (2021). Mi-croRNA panel in serum reveals novel diagnostic biomarkers for prostate can-cer. PeerJ, 9:e11441.
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21. Liu W, Wang X (2019). Prediction of func-tional microRNA targets by integrative modeling of microRNA binding and target expression data. Genome Biol, 20(1):18.
22. Agarwal V, Bell GW, Nam JW, Bartel DP (2015). Predicting effective microRNA target sites in mammalian mRNAs. Elife, 4:e05005.
23. Backes C, Kehl T, Stöckel D, et al (2017). miRPathDB: a new dictionary on mi-croRNAs and target pathways. Nucleic Acids Res, 45(Database issue):D90–6.
24. Thomas PD (2017). The Gene Ontology and the Meaning of Biological Function. Methods Mol Biol, 1446:15–24.
25. Kanehisa M, Furumichi M, Tanabe M, Sato Y, Morishima K (2017). KEGG: new perspectives on genomes, pathways, dis-eases and drugs. Nucleic Acids Res, 45(D1):D353–61.
26. Bader GD, Hogue CW (2003). An automat-ed method for finding molecular com-plexes in large protein interaction net-works. BMC Bioinformatics, 4(1):2.
27. Chandrashekar DS, Bashel B, Balasubra-manya SAH, et al (2017). UALCAN: A Portal for Facilitating Tumor Subgroup Gene Expression and Survival Analyses. Neoplasia, 19(8):649–58.
28. Vasaikar SV, Straub P, Wang J, Zhang B (2018). LinkedOmics: analyzing multi-omics data within and across 32 cancer types. Nucleic Acids Res, 46(D1):D956–63.
29. Barceló M, Castells M, Pérez-Riba M, Bas-sas L, Vigués F, Larriba S (2020). Seminal plasma microRNAs improve diagno-sis/prognosis of prostate cancer in men with moderately altered prostate-specific antigen. Am J Transl Res, 12(5):2041–51.
30. Porras-Quesada P, González-Cabezuelo JM, Sánchez-Conde V, et al (2022). Role of IGF2 in the Study of Development and Evolution of Prostate Cancer. Front Genet, 12:740641.
31. Wang C, Tian S, Zhang D, et al (2020). In-creased expression of microRNA-93 correlates with progression and progno-sis of prostate cancer. Medicine (Baltimore), 99(22):e18432.
32. Deng Z qun, Qian J, Liu F qiong, et al (2014). Expression level of miR-93 in formalin-fixed paraffin-embedded tis-sues of breast cancer patients. Genet Test Mol Biomarkers, 18(5):366–70.
33. Lyu X, Fang W, Cai L, et al (2014). TGFβR2 is a major target of miR-93 in nasopha-ryngeal carcinoma aggressiveness. Mol Cancer, 13:51.
34. Zhang H, Zhang J, Meng F, et al (2019). Mi-croRNA-93 promotes the tumorigenesis of osteosarcoma by targeting TIMP2. Bi-osci Rep, 39(8):BSR20191237.
35. Gao Y, Deng K, Liu X, et al (2019). Molec-ular mechanism and role of microRNA-93 in human cancers: A study based on bioinformatics analysis, meta-analysis, and quantitative polymerase chain reac-tion validation. J Cell Biochem, 120(4):6370–83.
36. Hu B, Mao Z, Du Q, et al (2019). miR-93-5p targets Smad7 to regulate the transform-ing growth factor-β1/Smad3 pathway and mediate fibrosis in drug-resistant prolactinoma. Brain Res Bull, 149:21–31.
37. Katsuya O, Hiromitsu H, Jinhua W, et al (2015). MicroRNA-93 activates c-Met/PI3K/Akt pathway activity in hepa-tocellular carcinoma by directly inhibit-ing PTEN and CDKN1A. Oncotarget, 6(5):3211-3224.
38. Jiang L, Wang C, Lei F, et al (2015). miR-93 Promotes Cell Proliferation in Gliomas through Activation of PI3K/Akt Signal-ing Pathway. Oncotarget, 6(10):8286–99.
39. Smith AL, Iwanaga R, Drasin DJ, et al (2012). The miR-106b-25 cluster targets Smad7, activates TGF-β signaling, and induces EMT and tumor initiating cell characteristics downstream of Six1 in human breast cancer. Oncogene, 31(50):5162–71.
40. Tang Q, Zou Z, Zou C, et al (2015). Mi-croRNA-93 suppress colorectal cancer development via Wnt/β-catenin path-way downregulating. Tumor Biol, 36(3):1701–10.
41. Qiu T, Grizzle WE, Oelschlager DK, Shen X, Cao X (2007). Control of prostate cell growth: BMP antagonizes androgen mi-togenic activity with incorporation of MAPK signals in Smad1. EMBO J, 26(2):346–57.
42. Qu F, Zheng J, Gan W, et al (2017). MiR-199a-3p suppresses proliferation and in-vasion of prostate cancer cells by target-ing Smad1. Oncotarget, 8(32):52465–73.
43. Wu J, Zhang M, Faruq O, et al (2021). SMAD1 as a biomarker and potential therapeutic target in drug-resistant mul-tiple myeloma. Biomark Res, 9(1):48.
44. Kobayashi A, Okuda H, Xing F, et al (2011). Bone morphogenetic protein 7 in dor-mancy and metastasis of prostate cancer stem-like cells in bone. J Exp Med, 208(13):2641–55.
2. Siegel RL, Miller KD, Fuchs HE, Jemal A (2021). Cancer Statistics, CA Cancer J Clin, 2021 71(1):7–33.
3. Gasinska A, Jaszczynski J, Rychlik U, Łuczynska E, Pogodzinski M, Palaczyn-ski M (2020). Prognostic Significance of Serum PSA Level and Telomerase, VEGF and GLUT-1 Protein Expression for the Biochemical Recurrence in Pros-tate Cancer Patients after Radical Pros-tatectomy. Pathol Oncol Res, 26(2):1049–56.
4. Chen D, Cabay RJ, Jin Y, Wang A, Lu Y, Shah-Khan M, et al (2013). MicroRNA Deregulations in Head and Neck Squa-mous Cell Carcinomas. J Oral Maxillofac Res, 4(1): e2.
5. Arantes LMRB, Laus AC, Melendez ME, et al (2017). MiR-21 as prognostic bi-omarker in head and neck squamous cell carcinoma patients undergoing an organ preservation protocol. Oncotarget, 8(6):9911–21.
6. Bartel DP (2004). MicroRNAs: genomics, biogenesis, mechanism, and function. Cell, 116(2):281–97.
7. Khan MM, Serajuddin M, Bharadwaj M (2023). Potential plasma microRNAs signature miR-190b-5p, miR-215-5p and miR-527 as non-invasive biomarkers for prostate cancer. Biomarkers, 28(2):227-237 .
8. Cao Z, Guo Y, Ao Y, Zhou S (2020). Dysregulated microRNAs in laryngeal cancer: a comprehensive meta-analysis using a robust rank aggregation ap-proach. Future Oncol, 16(33):2723–34.
9. Mitchell PS, Parkin RK, Kroh EM, et al (2008). Circulating microRNAs as stable blood-based markers for cancer detec-tion. Proc Natl Acad Sci USA, 105(30):10513–8.
10. Fendler A, Stephan C, Yousef GM, Kris-tiansen G, Jung K (2016). The transla-tional potential of microRNAs as bio-fluid markers of urological tumours. Nat Rev Urol, 13(12):734–52.
11. Choi N, Park J, Lee JS, et al (2015). miR-93/miR-106b/miR-375-CIC-CRABP1: a novel regulatory axis in prostate cancer progression. Oncotarget, 6(27):23533–47.
12. Ciszkowicz E, Porzycki P, Semik M, Kaznowska E, Tyrka M (2020). MiR-93/miR-375: Diagnostic Potential, Ag-gressiveness Correlation and Common Target Genes in Prostate Cancer. Int J Mol Sci, 21(16):5667.
13. Liu JJ, Zhang X, Wu XH (2018). miR-93 Promotes the Growth and Invasion of Prostate Cancer by Upregulating Its Target Genes TGFBR2, ITGB8, and LATS2. Mol Ther Oncolytics, 11:14–9.
14. Yang K, Gao ZY, Li TQ, et al (2019). An-ti-tumor activity and the mechanism of a green tea (Camellia sinensis) polysac-charide on prostate cancer. Int J Biol Macromol, 122:95–103.
15. Zedan AH, Osther PJS, Assenholt J, Madsen JS, Hansen TF (2020). Circulat-ing miR-141 and miR-375 are associated with treatment outcome in metastatic castration resistant prostate cancer. Sci Rep, 10(1):227.
16. Martínez-González LJ, Sánchez-Conde V, González-Cabezuelo JM, et al (2021). Identification of MicroRNAs as Viable Aggressiveness Biomarkers for Prostate Cancer. Biomedicines, 9(6):646.
17. Zhang S, Liu C, Zou X, et al (2021). Mi-croRNA panel in serum reveals novel diagnostic biomarkers for prostate can-cer. PeerJ, 9:e11441.
18. Page MJ, McKenzie JE, Bossuyt PM, et al (2021). The PRISMA 2020 statement: an updated guideline for reporting system-atic reviews. BMJ, 372:n71.
19. Rohatgi A (2022). WebPlotDigitizer User Manual Version 4.6. https://automeris.io/WebPlotDigitizer/userManual.pdf
20. Stang A (2010). Critical evaluation of the Newcastle-Ottawa scale for the assess-ment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol, 25(9):603–5.
21. Liu W, Wang X (2019). Prediction of func-tional microRNA targets by integrative modeling of microRNA binding and target expression data. Genome Biol, 20(1):18.
22. Agarwal V, Bell GW, Nam JW, Bartel DP (2015). Predicting effective microRNA target sites in mammalian mRNAs. Elife, 4:e05005.
23. Backes C, Kehl T, Stöckel D, et al (2017). miRPathDB: a new dictionary on mi-croRNAs and target pathways. Nucleic Acids Res, 45(Database issue):D90–6.
24. Thomas PD (2017). The Gene Ontology and the Meaning of Biological Function. Methods Mol Biol, 1446:15–24.
25. Kanehisa M, Furumichi M, Tanabe M, Sato Y, Morishima K (2017). KEGG: new perspectives on genomes, pathways, dis-eases and drugs. Nucleic Acids Res, 45(D1):D353–61.
26. Bader GD, Hogue CW (2003). An automat-ed method for finding molecular com-plexes in large protein interaction net-works. BMC Bioinformatics, 4(1):2.
27. Chandrashekar DS, Bashel B, Balasubra-manya SAH, et al (2017). UALCAN: A Portal for Facilitating Tumor Subgroup Gene Expression and Survival Analyses. Neoplasia, 19(8):649–58.
28. Vasaikar SV, Straub P, Wang J, Zhang B (2018). LinkedOmics: analyzing multi-omics data within and across 32 cancer types. Nucleic Acids Res, 46(D1):D956–63.
29. Barceló M, Castells M, Pérez-Riba M, Bas-sas L, Vigués F, Larriba S (2020). Seminal plasma microRNAs improve diagno-sis/prognosis of prostate cancer in men with moderately altered prostate-specific antigen. Am J Transl Res, 12(5):2041–51.
30. Porras-Quesada P, González-Cabezuelo JM, Sánchez-Conde V, et al (2022). Role of IGF2 in the Study of Development and Evolution of Prostate Cancer. Front Genet, 12:740641.
31. Wang C, Tian S, Zhang D, et al (2020). In-creased expression of microRNA-93 correlates with progression and progno-sis of prostate cancer. Medicine (Baltimore), 99(22):e18432.
32. Deng Z qun, Qian J, Liu F qiong, et al (2014). Expression level of miR-93 in formalin-fixed paraffin-embedded tis-sues of breast cancer patients. Genet Test Mol Biomarkers, 18(5):366–70.
33. Lyu X, Fang W, Cai L, et al (2014). TGFβR2 is a major target of miR-93 in nasopha-ryngeal carcinoma aggressiveness. Mol Cancer, 13:51.
34. Zhang H, Zhang J, Meng F, et al (2019). Mi-croRNA-93 promotes the tumorigenesis of osteosarcoma by targeting TIMP2. Bi-osci Rep, 39(8):BSR20191237.
35. Gao Y, Deng K, Liu X, et al (2019). Molec-ular mechanism and role of microRNA-93 in human cancers: A study based on bioinformatics analysis, meta-analysis, and quantitative polymerase chain reac-tion validation. J Cell Biochem, 120(4):6370–83.
36. Hu B, Mao Z, Du Q, et al (2019). miR-93-5p targets Smad7 to regulate the transform-ing growth factor-β1/Smad3 pathway and mediate fibrosis in drug-resistant prolactinoma. Brain Res Bull, 149:21–31.
37. Katsuya O, Hiromitsu H, Jinhua W, et al (2015). MicroRNA-93 activates c-Met/PI3K/Akt pathway activity in hepa-tocellular carcinoma by directly inhibit-ing PTEN and CDKN1A. Oncotarget, 6(5):3211-3224.
38. Jiang L, Wang C, Lei F, et al (2015). miR-93 Promotes Cell Proliferation in Gliomas through Activation of PI3K/Akt Signal-ing Pathway. Oncotarget, 6(10):8286–99.
39. Smith AL, Iwanaga R, Drasin DJ, et al (2012). The miR-106b-25 cluster targets Smad7, activates TGF-β signaling, and induces EMT and tumor initiating cell characteristics downstream of Six1 in human breast cancer. Oncogene, 31(50):5162–71.
40. Tang Q, Zou Z, Zou C, et al (2015). Mi-croRNA-93 suppress colorectal cancer development via Wnt/β-catenin path-way downregulating. Tumor Biol, 36(3):1701–10.
41. Qiu T, Grizzle WE, Oelschlager DK, Shen X, Cao X (2007). Control of prostate cell growth: BMP antagonizes androgen mi-togenic activity with incorporation of MAPK signals in Smad1. EMBO J, 26(2):346–57.
42. Qu F, Zheng J, Gan W, et al (2017). MiR-199a-3p suppresses proliferation and in-vasion of prostate cancer cells by target-ing Smad1. Oncotarget, 8(32):52465–73.
43. Wu J, Zhang M, Faruq O, et al (2021). SMAD1 as a biomarker and potential therapeutic target in drug-resistant mul-tiple myeloma. Biomark Res, 9(1):48.
44. Kobayashi A, Okuda H, Xing F, et al (2011). Bone morphogenetic protein 7 in dor-mancy and metastasis of prostate cancer stem-like cells in bone. J Exp Med, 208(13):2641–55.
| Files | ||
| Issue | Vol 52 No 11 (2023) | |
| Section | Review Article(s) | |
| DOI | https://doi.org/10.18502/ijph.v52i11.14026 | |
| Keywords | ||
| miR-93 Prostate Expression Meta-analysis Bioinformatics | ||
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How to Cite
1.
Gazzaz H, El Habchi M, El Feniche M, El Aatik Y, El Ouardi A, Ameur A, Dami A. Diagnostic and Prognostic Value of miR-93 in Prostate Cancer: A Meta-Analysis and Bioinformatics Analysis. Iran J Public Health. 2023;52(11):2260-2271.
