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miR-132 通过抑制抑癌基因 PTEN 促进人胰腺癌细胞的增殖、侵袭和迁移。

MiR-132 promotes the proliferation, invasion and migration of human pancreatic carcinoma by inhibition of the tumor suppressor gene PTEN.

机构信息

Department of Hepatopancreatobiliary Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610041, China.

Department of Hepatopancreatobiliary Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610041, China.

出版信息

Prog Biophys Mol Biol. 2019 Nov;148:65-72. doi: 10.1016/j.pbiomolbio.2017.09.019. Epub 2017 Sep 20.

Abstract

MicroRNA (miRNAs) emerges as key oncogene or tumor suppressor in a variety of cancers including pancreatic carcinoma. In this study, we detected the role of miR-132 in development and progression of pancreatic cancer and the underlying mechanism. First, the expression of miR-132 in pancreatic carcinoma and adjacent non-cancerous tissues were detected by qRT-PCR. Then, the role of miR-132 in biological function of pancreatic carcinoma cells was investigated. Our results identified that miR-132 was generally upregulated in pancreatic carcinoma, and phosphatase and tensin homolog (PTEN) was generally downregulated. miR-132 and PTEN were associated with advanced tumor size, lymph node metastasis and Tumor-Nodes-Metastases (TNM) stage of pancreatic carcinoma. Downregulation of miR-132 inhibited proliferation, migration and invasion of pancreatic carcinoma cells. In contrast, overexpression of miR-132 promoted proliferation, migration and invasion of pancreatic carcinoma cells. The luciferase reporter system demonstrated PTEN is a direct target of miR-132. Overexpression of PTEN abrogated the induction of miR-132 on proliferation, migration and invasion of pancreatic carcinoma cells. Taken together, miR-132 promotes the proliferation, invasion and migration of human pancreatic cancer by inhibition of PTEN, and could be a tumor oncogene in development and progression of pancreatic carcinoma, and might be a candidate prognostic biomarker and a promising target for new treatment of human pancreatic cancer.

摘要

MicroRNA (miRNAs) 作为多种癌症(包括胰腺癌)中的关键癌基因或肿瘤抑制因子而出现。在这项研究中,我们检测了 miR-132 在胰腺癌发生和发展中的作用及其潜在机制。首先,通过 qRT-PCR 检测胰腺癌及相邻非癌组织中 miR-132 的表达。然后,研究了 miR-132 对胰腺癌细胞生物学功能的作用。结果表明,miR-132 在胰腺癌中普遍上调,而磷酸酶和张力蛋白同源物(PTEN)普遍下调。miR-132 和 PTEN 与胰腺癌的肿瘤大小、淋巴结转移和肿瘤-淋巴结-转移(TNM)分期有关。下调 miR-132 抑制了胰腺癌细胞的增殖、迁移和侵袭。相反,过表达 miR-132 促进了胰腺癌细胞的增殖、迁移和侵袭。荧光素酶报告系统表明,PTEN 是 miR-132 的直接靶标。过表达 PTEN 可阻断 miR-132 对胰腺癌细胞增殖、迁移和侵袭的诱导作用。总之,miR-132 通过抑制 PTEN 促进人类胰腺癌的增殖、侵袭和迁移,可能是胰腺癌发生和发展中的肿瘤癌基因,并且可能成为人类胰腺癌的候选预后生物标志物和有前途的治疗靶点。

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