Department of Gynecology, The Affiliated Tumor Hospital of Harbin Medical University, 150 Haping Road, Nan Gang District, Harbin, 150081, Heilongjiang Province, China.
Biochem Biophys Res Commun. 2013 Nov 15;441(2):357-63. doi: 10.1016/j.bbrc.2013.10.052. Epub 2013 Oct 19.
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.
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。
