Wei Jin1, Fangjie Chen2, Kefeng Wang1, Yan Song1, Xiang Fei1, Bin Wu3. 1. Department of Urology, Shengjing Hospital of China Medical University, Shenyang, 110004, China. 2. Department of Medical Genetics, China Medical University, Shenyang, 110122, China. 3. Department of Urology, Shengjing Hospital of China Medical University, Shenyang, 110004, China. Electronic address: wubin_cmu@hotmail.com.
Abstract
BACKGROUND: To determine whether and how miR15a/16 regulate TGF-β signaling pathways during the progression of prostate cancer. METHODS: We used bioinformatics prediction, reporter gene assay, real-time PCR, Matrigel invasion assay and Western blot to dissect the molecular mechanism of how miR-15a/miR-16 may cause metastasis in prostate tumor. RESULTS: MiR-15a/16 targeted and inhibited the expression of endogenous Smad3 and ACVR2A proteins. The overexpression of miR15a/16 down-regulated p-smad3 expression, affected the expression of both MMP2 and E-cadherin, and down-regulated the expression of the EMT-mediated factors Snail and Twist in LNCaP prostate cancer cells. The overexpression of miR15a/16 decreased the invasion of LNCaP cells. MiR-15a/miR-16 cluster could reverse the invasion of activin A-mediated prostate cancer cells. After the inhibition of the activin/smad signaling pathway, the inhibitory effect of invasion in prostate cancer cells by miR-15a/miR-16 cluster disappeared. CONCLUSION: Our data indicated that miR15a/16 inhibited the components of TGF-β signaling pathways in LNCaP cell line, which might relate to the progression and metastasis of prostate cancer.
BACKGROUND: To determine whether and how miR15a/16 regulate TGF-β signaling pathways during the progression of prostate cancer. METHODS: We used bioinformatics prediction, reporter gene assay, real-time PCR, Matrigel invasion assay and Western blot to dissect the molecular mechanism of how miR-15a/miR-16 may cause metastasis in prostate tumor. RESULTS:MiR-15a/16 targeted and inhibited the expression of endogenous Smad3 and ACVR2A proteins. The overexpression of miR15a/16 down-regulated p-smad3 expression, affected the expression of both MMP2 and E-cadherin, and down-regulated the expression of the EMT-mediated factors Snail and Twist in LNCaP prostate cancer cells. The overexpression of miR15a/16 decreased the invasion of LNCaP cells. MiR-15a/miR-16 cluster could reverse the invasion of activin A-mediated prostate cancer cells. After the inhibition of the activin/smad signaling pathway, the inhibitory effect of invasion in prostate cancer cells by miR-15a/miR-16 cluster disappeared. CONCLUSION: Our data indicated that miR15a/16 inhibited the components of TGF-β signaling pathways in LNCaP cell line, which might relate to the progression and metastasis of prostate cancer.
Authors: Shaker A Mousa; Gennadi V Glinsky; Hung-Yun Lin; Osnat Ashur-Fabian; Aleck Hercbergs; Kelly A Keating; Paul J Davis Journal: Biomedicines Date: 2018-08-22