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miR-129-3p通过靶向调控Smad3对前列腺癌细胞生物学功能的影响

Effects of miR-129-3p on biological functions of prostate cancer cells through targeted regulation of Smad3.

作者信息

Jia Yunpeng, Gao Yu, Dou Jianguo

机构信息

Department of Urology Surgery, Gansu Provincial Hospital of TCM, Lanzhou, Gansu 730050, P.R. China.

Department of Urology Surgery, The Dazu District People's Hospital, Chongqing 402360, P.R. China.

出版信息

Oncol Lett. 2020 Feb;19(2):1195-1202. doi: 10.3892/ol.2019.11216. Epub 2019 Dec 13.

DOI:10.3892/ol.2019.11216
PMID:31966049
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6956156/
Abstract

Effects of miR-129-3p on the biological functions of prostate cancer cells through the targeted regulation of Smad3 were investigated. RT-PCR was used to detect the expression levels of miR-129-3p in prostate cancer tissues and cells and its target gene Smad3 mRNA determined by bioinformatics prediction. Correlation between miR-129-3p and Smad3 was analyzed. MTT assay, cell invasion detection, and apoptosis detection were conducted to detect the effects of miR-129-3p and Smad3 on the proliferation, invasion, and apoptosis of prostate cancer cells. The results of RT-qPCR showed that the expression level of miR-129-3p decreased but that of Smad3 increased in the prostate cancer tissue, and the expression levels of the two were significantly and negatively correlated. Additionally, the expression levels were closely related to the degree of tumor differentiation, TNM staging, and lymph node metastasis (P<0.05). Bioinformatics prediction and subsequent experiments proved that Smad3 was the direct target gene of miR-129-3p. Cell detection confirmed that the overexpression of miR-129-3p or the inhibition of Smad3 expression inhibited the proliferation and invasion of prostate cancer cells, promoting apoptosis, and increased the expression level of pro-apoptotic protein Bax, as well as decreased the expression level of anti-apoptotic protein Bcl-2. Inhibition of miR-129-3p expression had the opposite effect to overexpression. miR-129-3p, which may be a new and potential target for the treatment of prostate cancer, can inhibit the proliferation and invasion of prostate cancer cells and promote their apoptosis by directly targeting Smad3.

摘要

研究了miR-129-3p通过靶向调控Smad3对前列腺癌细胞生物学功能的影响。采用RT-PCR检测前列腺癌组织和细胞中miR-129-3p的表达水平,并通过生物信息学预测确定其靶基因Smad3 mRNA。分析miR-129-3p与Smad3之间的相关性。进行MTT法、细胞侵袭检测和凋亡检测,以检测miR-129-3p和Smad3对前列腺癌细胞增殖、侵袭和凋亡的影响。RT-qPCR结果显示,前列腺癌组织中miR-129-3p表达水平降低,而Smad3表达水平升高,二者表达水平呈显著负相关。此外,表达水平与肿瘤分化程度、TNM分期及淋巴结转移密切相关(P<0.05)。生物信息学预测及后续实验证明Smad3是miR-129-3p的直接靶基因。细胞检测证实,miR-129-3p过表达或Smad3表达抑制均能抑制前列腺癌细胞的增殖和侵袭,促进细胞凋亡,增加促凋亡蛋白Bax的表达水平,降低抗凋亡蛋白Bcl-2的表达水平。抑制miR-129-3p表达产生与过表达相反的作用。miR-129-3p可能是治疗前列腺癌的新的潜在靶点,可通过直接靶向Smad3抑制前列腺癌细胞的增殖和侵袭并促进其凋亡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/111f/6956156/5b2deadf6c41/ol-19-02-1195-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/111f/6956156/d06b83c05d17/ol-19-02-1195-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/111f/6956156/c95c745e0b4e/ol-19-02-1195-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/111f/6956156/baf3ffedf881/ol-19-02-1195-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/111f/6956156/5b2deadf6c41/ol-19-02-1195-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/111f/6956156/d06b83c05d17/ol-19-02-1195-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/111f/6956156/c95c745e0b4e/ol-19-02-1195-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/111f/6956156/baf3ffedf881/ol-19-02-1195-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/111f/6956156/5b2deadf6c41/ol-19-02-1195-g03.jpg

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