1. The putative tumour suppressor miR-1-3p modulates prostate cancer cell aggressiveness by repressing E2F5 and PFTK1
- Author
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Kun Tang, Xiao Yu, Huan-Lei Wu, Jia Hu, Zhangqun Ye, Shaogang Wang, and Sen-Mao Li
- Subjects
Male ,0301 basic medicine ,Cancer Research ,Proliferation ,Apoptosis ,Biology ,lcsh:RC254-282 ,Mice ,03 medical and health sciences ,Prostate cancer ,0302 clinical medicine ,Cell Movement ,LNCaP ,microRNA ,medicine ,Animals ,Humans ,Gene silencing ,Neoplasm Invasiveness ,Target gene ,Aged ,Cell Proliferation ,Aged, 80 and over ,E2F5 Transcription Factor ,Gene knockdown ,Research ,Prostatic Neoplasms ,Cell cycle ,Prognosis ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Xenograft Model Antitumor Assays ,Cell Cycle Gene ,Cyclin-Dependent Kinases ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,030104 developmental biology ,Oncology ,Gene Knockdown Techniques ,030220 oncology & carcinogenesis ,Disease Progression ,Cancer research ,Ectopic expression - Abstract
Background Previous studies report that miR-1-3p, a member of the microRNA-1 family (miR-1), and functions as a tumor suppressor in several different cancers. However, little is known regarding the biological role and intrinsic regulatory mechanisms of miR-1-3p in prostate cancer (PCa). Methods In this study, the expression levels of miR-1-3p were first examined in PCa cell lines and tumor tissues by RT-qPCR and bioinformatics. The in vitro and in vivo functional effect of miR-1-3p was examined further. A luciferase reporter assay was conducted to confirm target associations. Results We found that miR-1-3p was significantly downregulated in advanced PCa tissues and cell lines. Low miR-1-3p levels were strongly associated with aggressive clinicopathological features and poor prognosis in PCa patients. Ectopic expression of miR-1-3p in 22RV1 and LncaP cells was sufficient to prevent tumor cell growth and cell cycle progression in vitro and in vivo. Further mechanistic studies revealed that miR-1-3p could directly target the mRNA 3′- untranslated region (3′- UTR) of two central cell cycle genes, E2F5 and PFTK1, and could suppress their mRNA and protein expression. In addition, knockdown of E2F5 and PFTK1 mimicked the tumor-suppressive effects of miR-1-3p overexpression on PCa progression. Conversely, concomitant knockdown of miR-1-3p and E2F5 and PFTK1 substantially reversed the inhibitory effects of either E2F5 or PFTK1 silencing alone. Conclusion These data highlight an important role for miR-1-3p in the regulation of proliferation and cell cycle in the molecular etiology of PCa and indicate the potential for miR-1-3p in applications furthering PCa prognostics and therapeutics. Electronic supplementary material The online version of this article (10.1186/s13046-018-0895-z) contains supplementary material, which is available to authorized users.
- Published
- 2018