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TGF-β1-regulated miR-3691-3p targets E2F3 and PRDM1 to inhibit prostate cancer progression


1 Department of Pathology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou 215123, China
2 Department of Pathology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China
3 Collaborative Innovation Center of Clinical Immunology between Soochow University and Sihong People's Hospital, Sihong 223900, China
4 Department of Pathology, Sihong People's Hospital, Sihong 223900, China
5 Laboratory Animal Research Center, Soochow University School of Medicine, Suzhou 215123, China
6 Department of Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, China
7 Department of Pathology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China
8 Suzhou Key Laboratory of Tumor Microenvironment and Pathology, Soochow University, Suzhou 215006, China

Correspondence Address:
Shou-Li Wang,
Department of Pathology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou 215123; Suzhou Key Laboratory of Tumor Microenvironment and Pathology, Soochow University, Suzhou 215006
China
Yong-Sheng Zhang,
Department of Pathology, The Second Affiliated Hospital of Soochow University, Suzhou 215004
China
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/aja.aja_60_20

PMID: 33159025

Transforming growth factor-β1 (TGF-β1) acts as a tumor promoter in advanced prostate cancer (PCa). We speculated that microRNAs (miRNAs) that are inhibited by TGF-β1 might exert anti-tumor effects. To assess this, we identified several miRNAs downregulated by TGF-β1 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-β1-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-β1 contributes to the progression of PCa.


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