Department of Gynecology, Huadong Hospital, Fudan University, 221 Yan'an West Road, Shanghai, China.
Department of Gynecology, Huadong Hospital, Fudan University, 221 Yan'an West Road, Shanghai, China.
Biochem Biophys Res Commun. 2014 May 9;447(3):446-51. doi: 10.1016/j.bbrc.2014.04.027. Epub 2014 Apr 13.
MicroRNAs (miRNAs) are strongly implicated in tumorigenesis and metastasis. In this study, we showed significant upregulation of miR-181b in ovarian cancer tissues, compared with the normal ovarian counterparts. Forced expression of miR-181b led to remarkably enhanced proliferation and invasion of ovarian cancer cells while its knockdown induced significant suppression of these cellular events. The tumor suppressor gene, LATS2 (large tumor suppressor 2), was further identified as a novel direct target of miR-181b. Specifically, miR-181b bound directly to the 3'-untranslated region (UTR) of LATS2 and suppressed its expression. Restoration of LATS2 expression partially reversed the oncogenic effects of miR-181b. Our results indicate that miR-181b promotes proliferation and invasion by targeting LATS2 in ovarian cancer cells. These findings support the utility of miR-181b as a potential diagnostic and therapeutic target for ovarian cancer.
微小 RNA（miRNAs）在肿瘤发生和转移中起着重要作用。在这项研究中，我们发现卵巢癌组织中 miR-181b 的表达明显上调，与正常卵巢组织相比。强制表达 miR-181b 导致卵巢癌细胞的增殖和侵袭明显增强，而其敲低则显著抑制这些细胞事件。肿瘤抑制基因 LATS2（大肿瘤抑制因子 2）被进一步鉴定为 miR-181b 的一个新的直接靶基因。具体而言，miR-181b 直接结合到 LATS2 的 3'非翻译区（UTR）并抑制其表达。LATS2 表达的恢复部分逆转了 miR-181b 的致癌作用。我们的结果表明，miR-181b 通过靶向卵巢癌细胞中的 LATS2 促进增殖和侵袭。这些发现支持 miR-181b 作为卵巢癌潜在诊断和治疗靶点的应用。
