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微小RNA-34c通过靶向GIT1抑制乳腺癌的迁移和侵袭。

MicroRNA-34c Suppresses Breast Cancer Migration and Invasion by Targeting GIT1.

作者信息

Tao Wei-Yang, Wang Chun-Yang, Sun Yong-Hui, Su Yong-Hui, Pang Da, Zhang Guo-Qiang

机构信息

Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, China;; Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of Education, Harbin, China.

Key Laboratory of Cardiovascular Medicine Research (Harbin Medical University), Ministry of Education, Harbin, China;; Department of Urology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.

出版信息

J Cancer. 2016 Jul 25;7(12):1653-1662. doi: 10.7150/jca.14762. eCollection 2016.

Abstract

Abnormal expression of microRNAs plays important role in tumor metastasis. Migration and invasion of cancer cells accord for the metastasis and deterioration of breast cancer. However, the regulatory role of microRNAs in the invasion and migration of breast cancer cells has not completely understood yet. Here we found that microRNA-34c (miR-34c) was significantly downregulated in metastatic tissue of breast cancer. study showed that miR-34c negatively regulated GIT1 protein expression by binding to the 3'UTR of GIT1 mRNA. Consistently, GIT1 protein expression was found upregulated significantly in metastatic breast cancer. Moreover, miR-34c overexpression suppressed the expression of GIT1 protein, and this effect was restored by AMO-miR-34c in breast cancer cells. Overexpression of miR-34c suppressed cell migration and invasion in both MCF-7 and MDA-MD-231 breast cancer cells. Furthermore, knockdown of endogenous GIT1 expression reduced the migration and invasion of both two breast cancer cells. Collectively, miR-34c downregulation in breast cancer cells resulted in the upregulation of GIT1, which in turn enhanced the migration and invasion of breast cancer. This study highlights molecular mechanism of migration and invasion of breast cancer cells.

摘要

微小RNA的异常表达在肿瘤转移中起重要作用。癌细胞的迁移和侵袭与乳腺癌的转移和恶化一致。然而,微小RNA在乳腺癌细胞侵袭和迁移中的调控作用尚未完全明确。在此我们发现微小RNA-34c(miR-34c)在乳腺癌转移组织中显著下调。研究表明,miR-34c通过与GIT1 mRNA的3'非翻译区结合负调控GIT1蛋白表达。同样,在转移性乳腺癌中发现GIT1蛋白表达显著上调。此外,miR-34c过表达抑制了GIT1蛋白的表达,而在乳腺癌细胞中AMO-miR-34c可恢复这一效应。miR-34c过表达抑制了MCF-7和MDA-MD-231乳腺癌细胞的迁移和侵袭。此外,敲低内源性GIT1表达降低了两种乳腺癌细胞的迁移和侵袭。总体而言,乳腺癌细胞中miR-34c下调导致GIT1上调,进而增强了乳腺癌细胞的迁移和侵袭。本研究揭示了乳腺癌细胞迁移和侵袭的分子机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0df8/5039386/5b1e054ee14b/jcav07p1653g001.jpg

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