MicroRNA‐200a suppresses prostate cancer progression through BRD4/AR signaling pathway

Cancer Medicine

Rui Peng¹  Fang Fang²  Ming Chen³  Can Wang³  Zonghao You³  Bin Xu³  Han Guan⁴  Likai Mao⁵ 

[1] Department of Graduate School Bengbu Medical College Bengbu China;Department of Immunology Bengbu Medical College Bengbu China;Department of Urology Affliated Zhongda Hospital of Southeast University Nanjing China;Department of Urology The First Affiliated Hospital of Bengbu Medical College Bengbu China;Department of Urology The Second Affiliated Hospital of Bengbu Medical College Bengbu China;

关键词: androgen receptor;    BRD4;    miRNA;    prostate cancer;    signaling pathway;   

DOI  :  10.1002/cam4.2029

来源: DOAJ

【 摘 要 】

Abstract Prostate cancer is still considered a significant health care challenge worldwide due in part to the distinct transformation of androgen‐dependent prostate cancer (ADPC) into treatment‐refractory castration‐resistant prostate cancer (CRPC). Consequently, there is an urgent need to explore novel molecular mechanisms underlying treatment resistance in ADPC. Although numerous studies have alluded to the role of miR‐200a in several cancers, the biological significance of miR‐200a in prostate cancer remains unknown. After performing microarray analysis and reanalysis of the publicly available Memorial Sloan Kettering Cancer Center dataset, miR‐200a expression was found higher in ADPC tissues and its expression was positively associated with survival of CRPC patients. In vitro studies showed that miR‐200a overexpression in CRPC cells markedly suppressed cellular proliferation and facilitated apoptosis. In vivo studies indicated that overexpression of miR‐200a inhibited growth and metastasis of prostate cancer. The luciferase reporter assay demonstrated that BRD4 is a direct target gene of miR‐200a and it could reverse miR‐200a‐mediated biological effects in prostate cancer cells. Most importantly, our findings indicated that miR‐200a suppresses the progression of CRPC by inhibiting the activation of BRD4‐mediated AR signaling. This finding provides the foundation for the development of more personalized therapeutic approaches for CRPC patients.

【 授权许可】

Unknown