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Biochem Biophys Res Commun. 2014 Sep 26;452(3):746-52. doi: 10.1016/j.bbrc.2014.08.154. Epub 2014 Sep 6.

Metformin inhibits epithelial-mesenchymal transition in prostate cancer cells: involvement of the tumor suppressor miR30a and its target gene SOX4.

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Department of Pharmacy, Shandong Provincial Hospital, Shandong University, Jinan 250021, China.
Department of Pathology, School of Medicine, Shandong University, Jinan 250012, China; Research Center for Medicinal Biotechnology, Shandong Academy of Medicinal Sciences, Jinan 250012, China.
Department of Clinical Laboratory, The Fourth People's Hospital of Jinan, Jinan 250031, China.
Department of Pathology, School of Medicine, Shandong University, Jinan 250012, China.
Department of Pathology, School of Medicine, Shandong University, Jinan 250012, China; Department of Pathology, Qilu Hospital, Shandong University, Jinan 250012, China. Electronic address:


Tumor metastasis is the leading cause of mortality and morbidity of prostate cancer (PCa) patients. Epithelial-mesenchymal transition (EMT) plays a critical role in cancer progression and metastasis. Recent evidence suggested that diabetic patients treated with metformin have lower PCa risk and better prognosis. This study was aimed to investigate the effects of metformin on EMT in PCa cells and the possible microRNA (miRNA)-based mechanisms. MiRNAs have been shown to regulate various processes of cancer metastasis. We herein showed that metformin significantly inhibits proliferation of Vcap and PC-3 cells, induces G0/G1 cell cycle arrest and inhibits invasiveness and motility capacity of Vcap cells. Metformin could inhibit TGF-β-induced EMT in Vcap cells, as manifested by inhibition of the increase of N-cadherin (p=0.013), Vimentin (p=0.002) and the decrease of E-cadherin (p=0.0023) and β-catenin (p=0.034) at mRNA and protein levels. Notably, we demonstrated significant upregulation of miR30a levels by metformin (P<0.05) and further experiments indicated that miR30a significantly inhibits proliferation and EMT process of Vcap cells. Interestingly, we identified that SOX4, a previously reported oncogenic transcriptional factor and modulator of EMT, is a direct target gene of miR30a. Finally, we screened the expression of miR30a and SOX4 in 84 PCa cases with radical prostatectomy. Of note, SOX4 overexpression is significantly associated with decreased levels of miR30a in PCa cases. In all, our study suggested that inhibition of EMT by metformin in PCa cells may involve upregulation of miR30a and downregulation of SOX4.


Epithelial–mesenchymal transition; Metformin; Prostate cancer; SOX4; miR30a

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