期刊
ASIAN JOURNAL OF ANDROLOGY
卷 23, 期 2, 页码 -出版社
WOLTERS KLUWER MEDKNOW PUBLICATIONS
DOI: 10.4103/aja.aja_60_20
关键词
E2F transcription factor 3; miR-3691-3p; PR domain containing 1; with ZNF domain; prostate cancer; transforming growth factor-β 1
资金
- Shanghai Changning District Committee of Science and Technology [CNKW2016Y01]
- Shanghai Tongren Hospital Project [TRYJ201501]
- Suzhou Science and Technology Development Program [SYS201717]
- Second Affiliated Hospital of Soochow University Advance Research Program of the Natural Science Foundation of China [SDFEYGJ1705]
- Open project of Jiangsu State Key Laboratory of Radiation Medicine and Projection [GJS1963]
- Priority Academic Program Development of Jiangsu Higher Education Institutions
The study identified miR-3691-3p as a TGF-beta 1-regulated anti-oncogene in PCa, which inhibits progression by downregulating E2F3 and PRDM1. Overexpression of miR-3691-3p suppressed PCa cell proliferation, migration, and invasion, while promoting apoptosis. Treatment with miR-3691-3p agomir in PCa xenografts inhibited tumor growth and promoted cell apoptosis.
Transforming growth factor-beta 1 (TGF-beta 1) acts as a tumor promoter in advanced prostate cancer (PCa). We speculated that microRNAs (miRNAs) that are inhibited by TGF-beta 1 might exert anti-tumor effects. To assess this, we identified several miRNAs downregulated by TGF-beta 1 in PCa cell lines and selected miR-3691-3p for detailed analysis as a candidate anti-oncogene miRNA. miR-3691-3p was expressed at significantly lower levels in human PCa tissue compared with paired benign prostatic hyperplasia tissue, and its expression level correlated inversely with aggressive clinical pathological features. Overexpression of miR-3691-3p in PCa cell lines inhibited proliferation, migration, and invasion, and promoted apoptosis. The miR-3691-3p target genes E2F transcription factor 3 (E2F3) and PR domain containing 1, with ZNF domain (PRDM1) were upregulated in miR-3691-3p-overexpressing PCa cells, and silencing of E2F3 or PRDM1 suppressed PCa cell proliferation, migration, and invasion. Treatment of mice bearing PCa xenografts with a miR-3691-3p agomir inhibited tumor growth and promoted tumor cell apoptosis. Consistent with the negative regulation of E2F3 and PRDM1 by miR-3691-3p, both proteins were overexpressed in clinical PCa specimens compared with noncancerous prostate tissue. Our results indicate that TGF-beta 1-regulated miR-3691-3p acts as an anti-oncogene in PCa by downregulating E2F3 and PRDM1. These results provide novel insights into the mechanisms by which TGF-beta 1 contributes to the progression of PCa.
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