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微小RNA-144通过靶向胰岛素受体底物1抑制喉鳞状细胞癌的生长和转移。

miR-144 suppresses the growth and metastasis of laryngeal squamous cell carcinoma by targeting IRS1.

作者信息

Wu Xin, Cui Chang-Lei, Chen Wei-Lun, Fu Zhong-Ying, Cui Xiang-Yan, Gong Xu

机构信息

Department of Otorhinolaryngology-Head and Neck Surgery, The First Hospital of Jilin University 3302 Jilin Main Road, Changchun 130021, China.

Department of Anesthesiology, The First Hospital of Jilin University 3302 Jilin Main Road, Changchun 130021, China.

出版信息

Am J Transl Res. 2016 Jan 15;8(1):1-11. eCollection 2016.

Abstract

Increasing evidence has been suggested that microRNA-144 (miR-144) involved in tumor initiation, development and metastasis in various cancers. However, the biological roles and potential mechanisms of miR-144 in laryngeal squamous cell carcinoma (LSCC) remain unclear. In the present study, we discovered that miR-144 expression levels in LSCC tissues were significantly lower than those of adjacent normal tissues. Furthermore, overexpression of miR-144 in LSCC cells inhibited cell proliferation, colony formation, migration, and invasion in vitro. Consistently, stable overexpression of miR-144 suppressed the growth of LSCC cell xenografts in vivo. Bioinformatic algorithms and luciferase reporter assays confirmed that insulin receptor substrate 1 (IRS1) is a direct target of miR-144. Overexpreesion of miR-144 obviously decreased IRS1 expression thereby suppressing phosphatidylinositol 3-kinase (PI3K)/AKT pathway activation. Further functional studies suggested that downregulation of IRS1 had similar effects as that of miR-144 overexpression, and upregulation of IRS1 partially reversed the inhibitory effects of miR-144. These findings suggested that miR-144 functioned as a tumor suppressor in LSCC by targeting IRS1, and that miR-144 might serve as a potential target for LSCC treatment.

摘要

越来越多的证据表明,微小RNA-144(miR-144)参与多种癌症的肿瘤起始、发展和转移。然而,miR-144在喉鳞状细胞癌(LSCC)中的生物学作用和潜在机制仍不清楚。在本研究中,我们发现LSCC组织中miR-144的表达水平显著低于相邻正常组织。此外,在LSCC细胞中过表达miR-144可在体外抑制细胞增殖、集落形成、迁移和侵袭。同样,miR-144的稳定过表达在体内抑制了LSCC细胞异种移植瘤的生长。生物信息学算法和荧光素酶报告基因检测证实胰岛素受体底物1(IRS1)是miR-144的直接靶点。miR-144的过表达明显降低IRS1的表达,从而抑制磷脂酰肌醇3激酶(PI3K)/AKT途径的激活。进一步的功能研究表明,IRS1的下调与miR-144过表达具有相似的作用,而IRS1的上调部分逆转了miR-144的抑制作用。这些发现表明,miR-144通过靶向IRS1在LSCC中发挥肿瘤抑制作用,并且miR-144可能成为LSCC治疗的潜在靶点。

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