MicroRNA-31 functions as a tumor suppressor by regulating cell cycle and epithelial-mesenchymal transition regulatory proteins in liver cancer.
MicroRNA-31 functions as a tumor suppressor by regulating cell cycle and epithelial-mesenchymal transition regulatory proteins in liver cancer.
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MicroRNA-31通过调节肝癌中的细胞周期和上皮 - 间质转变蛋白来充当肿瘤抑制器。
DOI：
10.18632/oncotarget.3512
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发表时间：
2015-04-10
期刊：
影响因子：
--
通讯作者：
Nam SW
中科院分区：
文献类型：
--
作者：
Kim HS;Lee KS;Bae HJ;Eun JW;Shen Q;Park SJ;Shin WC;Yang HD;Park M;Park WS;Kang YK;Nam SW
microRNA-31（miR-31）是人类癌症中最常改变的microRNA之一，并且已经在多种肿瘤类型中检测到miR-31的改变的表达，但是miR-31的功能作用在不同肿瘤类型中仍然保持肿瘤抑制和致癌作用。miR-31的表达在一个大队列的肝细胞癌（HCC）患者中下调，并且miR-31的低表达与HCC患者的不良预后显著相关。miR-31模拟物的异位表达通过细胞周期蛋白的转录失调抑制HCC细胞生长。另外的研究证明miR-31通过抑制HCC细胞中的mRNA翻译直接抑制HDAC 2和CDK 2表达。我们还发现miR-31模拟物的异位表达通过选择性地调节上皮-间质转化（EMT）调节蛋白如N-钙粘蛋白、E-钙粘蛋白、波形蛋白和纤连蛋白来降低HCC细胞的转移潜能。来自化学诱导的大鼠肝癌模型的HCC组织验证了miR-31表达显著下调，并且这些细胞周期和EMT调节蛋白在大鼠肝癌中失调。总之，我们认为miR-31通过选择性调节细胞周期和EMT调节蛋白在人类肝癌发生中发挥肿瘤抑制剂的作用，为肝脏恶性肿瘤的分子治疗提供了新的靶点。
MicroRNA-31 (miR-31) is among the most frequently altered microRNAs in human cancers and altered expression of miR-31 has been detected in a large variety of tumor types, but the functional role of miR-31 still hold both tumor suppressive and oncogenic roles in different tumor types. MiR-31 expression was down-regulated in a large cohort of hepatocellular carcinoma (HCC) patients, and low expression of miR-31 was significantly associated with poor prognosis of HCC patients. Ectopic expression of miR-31 mimics suppressed HCC cell growth by transcriptional deregulation of cell cycle proteins. Additional study evidenced miR-31 directly to suppress HDAC2 and CDK2 expression by inhibiting mRNA translation in HCC cells. We also found that ectopic expression of miR-31 mimics reduced metastatic potential of HCC cells by selectively regulating epithelial-mesenchymal transition (EMT) regulatory proteins such as N-cadherin, E-cadherin, vimentin and fibronectin. HCC tissues derived from chemical-induced rat liver cancer models validated that miR-31 expression is significantly down-regulated, and that those cell cycle- and EMT-regulatory proteins are deregulated in rat liver cancer. Overall, we suggest that miR-31 functions as a tumor suppressor by selectively regulating cell cycle and EMT regulatory proteins in human hepatocarcinogenesis providing a novel target for the molecular treatment of liver malignancies.
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影响因子：
11.2
作者：
Lin PC;Chiu YL;Banerjee S;Park K;Mosquera JM;Giannopoulou E;Alves P;Tewari AK;Gerstein MB;Beltran H;Melnick AM;Elemento O;Demichelis F;Rubin MA
通讯作者：
Rubin MA
影响因子：
3.7
作者：
Noh JH;Jung KH;Kim JK;Eun JW;Bae HJ;Xie HJ;Chang YG;Kim MG;Park WS;Lee JY;Nam SW
通讯作者：
Nam SW
影响因子：
11.2
作者：
Liu, Chung-Ji;Tsai, Meng-Miao;Chang, Kuo-Wei
通讯作者：
Chang, Kuo-Wei
影响因子：
4.6
作者：
Karakatsanis, Andreas;Papaconstantinou, Ioannis;Voros, Dionysios
通讯作者：
Voros, Dionysios
影响因子：
--
作者：
Asangani IA;Harms PW;Dodson L;Pandhi M;Kunju LP;Maher CA;Fullen DR;Johnson TM;Giordano TJ;Palanisamy N;Chinnaiyan AM
通讯作者：
Chinnaiyan AM