miR-634 exhibits anti-tumor activities toward hepatocellular carcinoma via Rab1A and DHX33
miR-634 exhibits anti-tumor activities toward hepatocellular carcinoma via Rab1A and DHX33
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miR-634 通过 Rab1A 和 DHX33 对肝细胞癌表现出抗肿瘤活性
DOI：
10.1016/j.molonc.2016.09.001
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发表时间：
2016-12-01
影响因子：
6.6
通讯作者：
Zhang, Mei-Fang
中科院分区：
文献类型：
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作者：
Zhang, Chris Zhiyi;Cao, Yun;Zhang, Mei-Fang
microRNA 的失调会导致肝细胞癌 (HCC) 的异常生长。在这里，我们发现 HCC 中 miR-634 表达经常降低。低miR-634表达与较大的肿瘤大小、较差的肿瘤分化、晚期TNM分期、血管侵犯、缺乏肿瘤包膜和不利的总生存期显着相关。 miR-634 的过度表达显着减弱细胞活力、集落形成、肿瘤生长和转移，而 miR-634 抑制则导致相反的表型。此外，重新引入 miR-634 会在体外和体内诱导细胞凋亡。从机制上讲，miR-634 通过直接结合 Rab1A 和 DHX33 基因的 3'-UTR 来抑制这两个基因的表达。在临床样本中，Rab1A或DHX33的表达与miR-634呈负相关。 Rab1A 或 DHX33 的重新表达消除了 miR-634 介导的细胞增殖和迁移抑制。总的来说，我们的数据表明 miR-634 在 HCC 中具有肿瘤抑制作用。新发现的 miR-634/Rab1A 或 miR-634/DHX33 轴可作为临床管理的潜在治疗靶点。 (C) 2016 年欧洲生化学会联合会。由 Elsevier B.V. 出版。保留所有权利。
Deregulation of microRNAs contributes to the aberrant growth of hepatocellular carcinoma (HCC). Here, we showed that miR-634 expression was frequently decreased in HCC. Low miR-634 expression was significantly associated with larger tumor size, poorer tumor differentiation, advanced TNM stage, vascular invasion, absence of tumor capsule and unfavorable overall survival. Overexpression of miR-634 markedly attenuated cell viability, colony formation, tumor growth and metastasis, whereas miR-634 inhibition resulted in the opposite phenotypes. Furthermore, re-introduction of miR-634 induced cell apoptosis in vitro and in vivo. Mechanistically, miR-634 inhibited the expression of Rab1A and DHX33 via directly binding to the 3'-UTR of both genes. In clinical samples, the expression of Rab1A or DHX33 was reversely correlated with miR-634. Re-expression of Rab1A or DHX33 abrogated the miR-634-mediated inhibition of cell proliferation and migration. Collectively, our data suggest a tumor suppressor role of miR-634 in HCC. The newly identified miR-634/Rab1A or miR-634/DHX33 axis serves as a potential therapeutic target for the clinical management. (C) 2016 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.