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微小RNA-542-3p通过靶向调控皮层肌动蛋白抑制结肠癌细胞的生长和侵袭。

miR-542-3p inhibits the growth and invasion of colorectal cancer cells through targeted regulation of cortactin.

作者信息

Long Hao-Cheng, Gao Xia, Lei Chang-Jiang, Zhu Bin, Li Lei, Zeng Cheng, Huang Jian-Bin, Feng Jia-Rui

机构信息

Department of General Surgery, The Fifth Hospital of Wuhan, Wuhan, Hubei 430050, P.R. China.

Department of Oncology, The Fifth Hospital of Wuhan, Wuhan, Hubei 430050, P.R. China.

出版信息

Int J Mol Med. 2016 Apr;37(4):1112-8. doi: 10.3892/ijmm.2016.2505. Epub 2016 Feb 25.

Abstract

Colorectal cancer is one of the most common malignancies. Previous studies have reported that cortactin (CTTN) is often overexpressed in tumors and is associated with metastasis and poor prognosis of patients. The abnormal expression of microRNAs (miRNAs or miRs) is closely related to the development and progression of various types of cancer, including colorectal cancer. However, little is known about the miRNAs targeting cortactin. In the present study, prediction using biological software revealed that cortactin has binding sites for miR-542-3p. Transfection with miR-542-3p mimic demonstrated that miR‑542-3p reduced the expression of cortactin in colorectal cancer cells. Dual luciferase reporter assays further demonstrated that miR-542-3p regulated cortactin in a targeted manner and that miR-542-3p expression was significantly downregulated in colorectal cancer cells. A cell proliferation assay and Transwell migration assay were undertaken: we noted that miR‑542-3p inhibited the proliferation and invasion of colorectal cancer cells while promoting their apoptosis. By contrast, cortactin acted antagonistically. When co-transfected with miR-542-3p mimic and CTTN overexpression vector, the inhibitory effect of miR-542-3p was blocked. This indicates that miR-542-3p regulates CTTN in a targeted manner to modulate the growth and invasion of colorectal cancer cells. The present study thus provides new targets for the prevention and treatment of colorectal cancer.

摘要

结直肠癌是最常见的恶性肿瘤之一。以往研究报道,皮层肌动蛋白(CTTN)在肿瘤中常过度表达,且与患者的转移及不良预后相关。微小RNA(miRNA或miR)的异常表达与包括结直肠癌在内的各种类型癌症的发生和发展密切相关。然而,关于靶向皮层肌动蛋白的miRNA却知之甚少。在本研究中,使用生物软件进行预测发现皮层肌动蛋白具有miR-542-3p的结合位点。用miR-542-3p模拟物转染表明,miR-542-3p可降低结直肠癌细胞中皮层肌动蛋白的表达。双荧光素酶报告基因检测进一步证明,miR-542-3p以靶向方式调控皮层肌动蛋白,且miR-542-3p在结直肠癌细胞中的表达显著下调。进行了细胞增殖试验和Transwell迁移试验:我们注意到miR-542-3p抑制结直肠癌细胞的增殖和侵袭,同时促进其凋亡。相比之下,皮层肌动蛋白则起拮抗作用。当与miR-542-3p模拟物和CTTN过表达载体共转染时,miR-542-3p的抑制作用被阻断。这表明miR-542-3p以靶向方式调控CTTN,从而调节结直肠癌细胞的生长和侵袭。本研究因此为结直肠癌的预防和治疗提供了新的靶点。

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