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MicroRNA-596 is epigenetically inactivated and suppresses prostatic cancer cell growth and migration via regulating Wnt/β-catenin signaling

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Abstract

Objectives

Although studies have reported that miR-596 extensively participates in multiple cancer progression, the biological mechanisms and effects of miR-596 in prostatic cancer remain unclear. The literature is aimed to reveal the function and possible molecular mechanisms of miR-596 in prostatic cancer carcinogenesis.

Materials and methods

qRT-PCR was applied to examine miR-596 expression in prostatic cancer cell lines and samples, also methylation-specific PCR was used to detect the methylation status of the promoter CpG islands in prostatic cancer samples. Meanwhile, the tumor-related effects of miR-596 were detected via cell viability, clone formation assay, migration assay, flow cytometric and AO/EB assay. qRT-PCR and Western blots were applied to investigate the function of miR-596 on malignant behavior in prostatic cancer cells.

Results

We found that miR-596 mRNA was decreased in prostatic cancer samples and cell lines. miR-596 mRNA level was also correlated to cancer stage, Gleason scores, while miR-596 promoter methylation was related to cancer tumor stage, Gleason score and preoperative PSA levels. miR-596 inhibited the cell growth and activity by causing cell apoptosis, and also suppressed the migration of prostatic cancer cells by revealing the epithelial-mesenchymal transition process. In addition, Western blot indicates that miR-596 overexpression deregulated Wnt/β-catenin signaling, by restraining phosphorylation levels of β-catenin and expression levels of downstream targets.

Conclusions

In summary, this research indicates that miR-596 overexpression could be potentially useful in the cell growth and migration of prostatic cancer and serves as a potential molecular marker in prostatic cancer.

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References

  1. Ghagane SC, Nerli RB, Hiremath MB, et al. Incidence of prostate cancer at a single tertiary care center in North Karnataka. Indian J Cancer. 2016;53:429–31.

    CAS  PubMed  Google Scholar 

  2. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2018;68:7–30.

    Article  Google Scholar 

  3. Basu S, Majumder S, Bhowal A, et al. A study of molecular signals deregulating mismatch repair genes in prostate cancer compared to benign prostatic hyperplasia. PLoS ONE. 2015;10:e0125560.

    Article  Google Scholar 

  4. Zhao Y, Zhang G, Wei M, et al. The tumor-suppressing effects of QKI-5 in prostate cancer: a novel diagnostic and prognostic protein. Cancer Biol Ther. 2014;15:108–18.

    Article  CAS  Google Scholar 

  5. Li S, Pu T, Xiao L, et al. Screening of recurrence related microrna in ductal carcinoma in situ and functional study of MicroRNA-654-5p. J Breast Cancer. 2019;22:52–66.

    Article  Google Scholar 

  6. Li T, Zhou W, Li Y, Gan Y, et al. MiR-4524b-5p/WTX/β-catenin axis functions as a regulator of metastasis in cervical cancer. PLoS ONE. 2019;14:e0214822.

    Article  CAS  Google Scholar 

  7. Ying L, Chen Q, Wang Y, et al. Upregulated MALAT-1 contributes to bladder cancer cell migration by inducing epithelial-to-mesenchymal transition. Mol Biosyst. 2012;8:2289–94.

    Article  CAS  Google Scholar 

  8. Pereira DM, Rodrigues CMP. iRNAs as modulators of EGFR therapy in colorectal cancer. Adv Exp Med Biol. 2018;1110:133–47.

    Article  CAS  Google Scholar 

  9. Liu SM, Lin CH, Lu J, et al. miR-596 modulates melanoma growth by regulating cell survival and death. J Invest Dermatol. 2018;138:911–21.

    Article  CAS  Google Scholar 

  10. Li H. Exploration of alternative mechanism for MiR-596-mediated down-regulation of LGALS3BP in oral squamous cell carcinoma. Kokubyo Gakkai Zasshi. 2015;82:55–61.

    PubMed  Google Scholar 

  11. Zhang Z, Dai DQ. MicroRNA-596 acts as a tumor suppressor in gastric cancer and is upregulated by promotor demethylation. World J Gastroenterol. 2019;25:1224–37.

    Article  CAS  Google Scholar 

  12. Kim JH, Seo BS. How to calculate sample size and why. Clin Orthop Surg. 2013;5(3):235–42.

    Article  Google Scholar 

  13. Vanz ALS, Renard G, Palma MS, et al. Human granulocyte colony stimulating factor (hG-CSF): cloning, overexpression, purification and characterization. Microb Cell Fact. 2008;7:13.

    Article  Google Scholar 

  14. Shan Y, Ying R, Jia Z, et al. LINC00052 promotes gastric cancer cell proliferation and metastasis via activating the wnt/β-catenin signaling pathway. Oncol Res. 2017;25:1589–99.

    Article  Google Scholar 

  15. Liu B, Chen W, Cao G, et al. MicroRNA-27b inhibits cell proliferation in oral squamous cell carcinoma by targeting FZD7 and Wnt signaling pathway. Arch Oral Biol. 2017;83:92–6.

    Article  CAS  Google Scholar 

  16. Wang JJ, Li ZF, Li XJ, et al. Effects of microRNA-136 on melanoma cell proliferation, apoptosis, and epithelial-mesenchymal transition by targetting PMEL through the Wnt signaling pathway. Biosci Rep. 2017;37:BSR20170743.

    Article  CAS  Google Scholar 

  17. Leighton X, Bera A, Eidelman O, et al. Tissue microarray analysis delineate potential prognostic role of Annexin A7 in prostate cancer progression. PLoS ONE. 2018;13:e0205837.

    Article  Google Scholar 

  18. Nasser MI, Han T, Adlat S, et al. Inhibitory effects of Schisandrin B on human prostate cancer cells. Oncol Rep. 2019;41:677–85.

    CAS  PubMed  Google Scholar 

  19. Ren W, Wang D, Li C, et al. Capn4 expression is modulated by microRNA-520b and exerts an oncogenic role in prostate cancer cells by promoting Wnt/β-catenin signaling. Biomed Pharmacother. 2018;8:467–75.

    Article  Google Scholar 

  20. Zhao YS, Yang WC, Xin HW, et al. MiR-182-5p Knockdown Targeting PTEN Inhibits cell proliferation and invasion of breast cancer cells. Yonsei Med J. 2019;60:148–57.

    Article  CAS  Google Scholar 

  21. Chen X, Wang A. Clinical significance of miR-195 in hepatocellular carcinoma and its biological function in tumor progression. Onco Targets Ther. 2019;12:527–34.

    Article  CAS  Google Scholar 

  22. Zhang L, Zhang T, Deng Z, et al. MicroRNA-3653 inhibits the growth and metastasis of hepatocellular carcinoma by inhibiting ITGB1. Oncol Rep. 2019;41:1669–77.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Yao Y, Zhou Y, Fu X. miR-671-3p is downregulated in non-small cell lung cancer and inhibits cancer progression by directly targeting CCND2. Mol Med Rep. 2019;19:2407–12.

    CAS  PubMed  Google Scholar 

  24. Wang B, Lu FY, Shi RH, et al. MiR-26b regulates 5-FU-resistance in human colorectal cancer via down-regulation of Pgp. Am J Cancer Res. 2018;8:2518–27.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Qu F, Cui X, Hong Y, et al. MicroRNA-185 suppresses proliferation, invasion, migration, and tumorigenicity of human prostate cancer cells through targeting androgen receptor. Mol Cell Biochem. 2013;377:121–30.

    Article  CAS  Google Scholar 

  26. Thieu W, Tilki D, de Vere WR, et al. The role of microRNA in castration-resistant prostate cancer. Urol Oncol. 2014;32:517–23.

    Article  CAS  Google Scholar 

  27. Li J, Yang X, Guan H, et al. Exosome-derived microRNAs contribute to prostate cancer chemoresistance. Int J Oncol. 2016;49:838–46.

    Article  CAS  Google Scholar 

  28. Lin YL, Deng QK, Wang YH, et al. Aberrant protocadherin17 (PCDH17) methylation in serum is a potential predictor for recurrence of early-stage prostate cancer patients after radical prostatectomy. Med Sci Monit. 2015;21:3955–3690.

    Article  CAS  Google Scholar 

  29. Lin YL, Wang YP, Li HZ, et al. Aberrant promoter methylation of PCDH17 (Protocadherin 17) in serum and its clinical significance in renal cell carcinoma. Med Sci Monit. 2017;23:3318–23.

    Article  Google Scholar 

  30. Guo YL, Shan BE, Guo W, et al. Aberrant methylation of DACT1 and DACT2 are associated with tumor progression and poor prognosis in esophageal squamous cell carcinoma. J Biomed Sci. 2017;24:6–12.

    Article  Google Scholar 

  31. Wang G, Chen H, Liu J. The long noncoding RNA LINC01207 promotes the proliferation of lung adenocarcinoma. Am J Cancer Res. 2015;5:3162–73.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Yin W, Chen J, Wang G, et al. MicroRNA-106b functions as an oncogene and regulates tumor viability and metastasis by targeting LARP4B in prostate cancer. Mol Med Rep. 2019;20:951–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Ou J, Guan D, Yang Y. Non-contact co-culture with human vascular endothelial cells promotes epithelial-to-mesenchymal transition of cervical cancer SiHa cells by activating the NOTCH1/LOX/SNAIL pathway. Cell Mol Biol Lett. 2019;24:39.

    Article  Google Scholar 

  34. Chen T, Zhou L, Zhou Y, et al. HJURP promotes epithelial-to-mesenchymal transition via upregulating SPHK1 in hepatocellular carcinoma. Int J Biol Sci. 2019;15:1139–47.

    Article  CAS  Google Scholar 

  35. Klos KS, Kim S, Alexander CM. Genotoxic exposure during juvenile growth of mammary gland depletes stem cell activity and inhibits Wnt signaling. PLoS ONE. 2012;7:e49902.

    Article  CAS  Google Scholar 

  36. Ma K, Cao B, Guo M. The detective, prognostic, and predictive value of DNA methylation in human esophageal squamous cell carcinoma. Clin Epigenetics. 2016;8:43.

    Article  Google Scholar 

  37. Wang D, Lu G, Shao Y, Xu D. MiR-182 promotes prostate cancer progression through activating Wnt/β-catenin signal pathway. Biomed Pharmacother. 2018;99:334–9.

    Article  CAS  Google Scholar 

  38. Yu Z, Wang Z, Li F, et al. miR-138 modulates prostate cancer cell invasion and migration via Wnt/β-catenin pathway. Mol Med Rep. 2018;17:3140–5.

    CAS  PubMed  Google Scholar 

  39. Zhang K, Guo Y, Wang X, et al. WNT/β-catenin directs self-renewal symmetric cell division of hTERThigh prostate cancer stem cells. Cancer Res. 2017;77:2534–47.

    Article  CAS  Google Scholar 

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Funding

Key projects of Chongqing Health Commission, 2016ZDXM031 and Chongqing Health Committee, 2020MSXM015.

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Authors and Affiliations

  1. Chongqing University Cancer Hospital, Chongqing, China

    J. Dai, G. Yuan, Y. Li & H. Zhou

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  1. J. Dai
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  2. G. Yuan
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  3. Y. Li
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  4. H. Zhou
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Corresponding author

Correspondence to H. Zhou.

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The authors declare that they have no competing interests.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Dai, J., Yuan, G., Li, Y. et al. MicroRNA-596 is epigenetically inactivated and suppresses prostatic cancer cell growth and migration via regulating Wnt/β-catenin signaling. Clin Transl Oncol 23, 1394–1404 (2021). https://doi.org/10.1007/s12094-020-02536-y

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  • DOI: https://doi.org/10.1007/s12094-020-02536-y

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