miR-141-3p Suppresses Expression of Androgen Receptors and Functions as a Tumor Suppressor Gene in Prostate Carcinogenesis
| Autor: | Huan Chen, Guomei Ru, Wanlei Yang, Tingzhang Wang, Chunjiao Song, Qian‐Nan Ding |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Tumor suppressor gene Cell growth Biology medicine.disease_cause medicine.disease Androgen receptor 03 medical and health sciences Open reading frame Prostate cancer 030104 developmental biology 0302 clinical medicine medicine.anatomical_structure Endocrinology Prostate 030220 oncology & carcinogenesis Internal medicine microRNA medicine Cancer research Carcinogenesis |
| Zdroj: | International Journal of Clinical Medicine. :55-72 |
| ISSN: | 2158-2882 2158-284X |
| DOI: | 10.4236/ijcm.2017.82006 |
| Popis: | Background: Prostate cancer (PCa) is a leading cause of tumor mortality in Western societies. In China, the PCa mortality rate is increasing yearly. Androgen receptors (ARs) and microRNAs (miRNAs) play central roles in prostate carcinogenesis and progression. Methods: To characterize the underlying molecular mechanisms, we compared the miRNA profiles of early PCa (G ≤ 7), advanced PCa (G > 7) and non-tumor prostate tissues using deep-sequencing. The target genes of differentially expressed miRNAs were predicted by bioinformatics analysis and confirmed by luciferase reporter assays and Western blot (WB) and quantitative reverse transcription-PCR (qRT-PCR) analyses. Finally, we performed in vitro functional studies by inducing or inhibiting miR-141-3p expression using an artificial mimic or inhibitor. Results: A computational search implicated the open reading frame (ORF) of AR mRNA as a potential miR-141-3p target site. The qRT-PCR, WB and luciferase reporter assays revealed a reverse regulatory effect of miR-141-3p on AR. Mutation of the potential miR-141-3p binding site in the AR ORF resulted in a loss of responsiveness to the corresponding miRNA. Moreover, miR-141-3p expression levels were unchanged in early PCas, but were obviously increased in advanced PCas. MiR-141-3p overexpression inhibited RWPE-1 cell proliferation, mobility, and prohibited the entry of cells into the G2-S-M phase; miR-141-3p inhibition had the inverse effects. At the same time, we tested miR-141-3p’s functions in PC-3 and VCaP prostate cancer cell lines. Conclusions: Taken together, our results indicate that miR-141-3p targets AR and its downstream signaling pathways, and functions as a tumor suppressor miR in PCa carcinogenesis by suppressing cell growth and mobility, but the effect is not significant in maglinant PCas. MiR-141-3p is implicated as a novel therapeutic target for early PCa. |
| Databáze: | OpenAIRE |
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