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miR-137 通过靶向 AEG-1 抑制卵巢癌细胞生长。

miR-137 suppresses cell growth in ovarian cancer by targeting AEG-1.

机构信息

Department of Gynecology, The Affiliated Tumor Hospital of Harbin Medical University, 150 Haping Road, Nan Gang District, Harbin, 150081, Heilongjiang Province, China.

出版信息

Biochem Biophys Res Commun. 2013 Nov 15;441(2):357-63. doi: 10.1016/j.bbrc.2013.10.052. Epub 2013 Oct 19.

Abstract

Astrocyte elevated gene-1 (AEG-1) is an oncogene overexpressed in multiple types of human cancers including ovarian cancer (OC). However, the underlying mechanism of AEG-1 up-regulation in OC is not well understood. In this study, we showed that miR-137 downregulated AEG-1 expression through interaction with its 3' untranslated region (3'UTR) and that miR-137 expression was inversely correlated with AEG-1 levels in OC specimens. Similar to the downregulation of AEG-1, overexpression of miR-137 in OC cell lines decreased in vitro cell growth, clonogenicity, and also induced G1 arrest. Importantly, miR-137 overexpression suppressed in vivo tumor growth in nude mice models. Furthermore, we found that restoring the AEG-1 (without the 3'UTR) significantly rescued miR-137-induced cell growth inhibition and cell-cycle arrest. Taken together, these findings indicate that miR-137 functions as a tumor suppressor by inhibition of AEG-1. These molecules might be targets for prevention or treatment of OC.

摘要

星形细胞上调基因-1(AEG-1)是一种在多种人类癌症中过表达的癌基因,包括卵巢癌(OC)。然而,AEG-1 在 OC 中上调的潜在机制尚不清楚。在这项研究中,我们表明 miR-137 通过与其 3'非翻译区(3'UTR)相互作用而下调 AEG-1 表达,并且 miR-137 的表达与 OC 标本中 AEG-1 水平呈负相关。与 AEG-1 的下调相似,OC 细胞系中 miR-137 的过表达降低了体外细胞生长、集落形成能力,并且还诱导了 G1 期阻滞。重要的是,miR-137 过表达抑制了裸鼠模型中的体内肿瘤生长。此外,我们发现恢复 AEG-1(无 3'UTR)可显著挽救 miR-137 诱导的细胞生长抑制和细胞周期阻滞。总之,这些发现表明 miR-137 通过抑制 AEG-1 发挥肿瘤抑制作用。这些分子可能是预防或治疗 OC 的靶点。

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