MicroRNA-130b promotes cell aggressiveness by inhibiting peroxisome proliferator-activated receptor gamma in human hepatocellular carcinoma.
MicroRNA-130b promotes cell aggressiveness by inhibiting peroxisome proliferator-activated receptor gamma in human hepatocellular carcinoma.
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MicroRNA-130b 通过抑制人肝细胞癌中的过氧化物酶体增殖物激活受体 γ 来促进细胞侵袭性。
DOI：
10.3390/ijms151120486
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发表时间：
2014-11-07
影响因子：
5.6
通讯作者：
Liu Q
中科院分区：
文献类型：
--
作者：
Tu K;Zheng X;Dou C;Li C;Yang W;Yao Y;Liu Q
miRNA-130 b（miR-130 b）被认为是一种新的肿瘤相关的miRNA，并且已经发现在肿瘤中显著失调。本研究发现miR-130 b在肝细胞癌（HCC）组织中的表达水平明显高于非肿瘤组织。此外，miR-130 b在侵袭性和复发性肿瘤组织中以显著更高的水平表达。临床分析显示，miR-130 b高表达与HCC静脉浸润、Edmondson-Steiner分级高、TNM分期高相关。与未转化的肝细胞系（LO 2）相比，在所有HCC细胞系（HepG 2、SMMC-7721、Huh 7、Hep 3B和MHCC 97 H）中均观察到miR-130 b表达升高。此外，在HCC组织中观察到miR-130 b与E-cadherin之间呈负相关，而与Vimentin之间呈正相关。下调miR-130 b表达可降低Hep 3B和MHCC 97 H细胞的侵袭和迁移。肝癌组织中过氧化物酶体增殖物激活受体γ（PPAR-γ）与miR-130 b表达呈负相关。此外，下调miR-130 b恢复了HCC细胞中的PPAR-γ表达，随后抑制了上皮-间质转化（EMT）。我们在体外将PPARγ鉴定为HCC中miR-130 b的直接靶点。值得注意的是，在MHCC 97 H细胞中，PPAR-γ敲低消除了miR-130 b抑制的EMT的下调。结论：miR-130 b可能通过抑制PPAR-γ进而诱导EMT，促进HCC细胞的迁移和侵袭。
MircroRNA-130b (miR-130b) is proposed as a novel tumor-related miRNA and has been found to be significantly dysregulated in tumors. In this study, the expression level of miR-130b was found to be obviously higher in hepatocellular carcinoma (HCC) tissues than that in nontumor tissues. Further, miR-130b was expressed at significantly higher levels in aggressive and recurrent tumor tissues. Clinical analysis indicated that high-expression of miR-130b was prominently correlated with venous infiltration, high Edmondson-Steiner grading and advanced tumor-node-metastasis (TNM) tumor stage in HCC. Elevated miR-130b expression was observed in all HCC cell lines (HepG2, SMMC-7721, Huh7, Hep3B and MHCC97H) as compared with that in a nontransformed hepatic cell line (LO2). Furthermore, an inverse correlation between miR-130b and E-cadherin and a positive correlation between miR-130b and Vimentin were observed in HCC tissues. Down-regulation of miR-130b expression reduced invasion and migration in both Hep3B and MHCC97H cells. Peroxisome proliferator-activated receptor gamma (PPAR-γ) was inversely correlated with miR-130b expression in HCC tissues. In addition, down-regulation of miR-130b restored PPAR-γ expression and subsequently suppressed epithelial-mesenchymal transition (EMT) in HCC cells. We identified PPARγ as a direct target of miR-130b in HCC in vitro. Notably, PPAR-γ knockdown abolished down-regulation of miR-130b-inhibited EMT in MHCC97H cells. In conclusion, miR-130b may promote HCC cell migration and invasion by inhibiting PPAR-γ and subsequently inducing EMT.
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影响因子：
8.8
作者：
Shen, B.;Chu, E. S. H.;Zhao, G.;Man, K.;Wu, C-W;Cheng, J. T. Y.;Li, G.;Nie, Y.;Lo, C. M.;Teoh, N.;Farrell, G. C.;Sung, J. J. Y.;Yu, J.
通讯作者：
Yu, J.
影响因子：
64.8
作者：
Lu, J;Getz, G;Golub, TR
通讯作者：
Golub, TR
影响因子：
2.9
作者：
Liu AM;Yao TJ;Wang W;Wong KF;Lee NP;Fan ST;Poon RT;Gao C;Luk JM
通讯作者：
Luk JM
人肝细胞癌中Fbxw7表达及其与c-Myc、cyclin E、p53表达的相关性评价
影响因子：
4.2
作者：
Tu, Kangsheng;Zheng, Xin;Liu, Qingguang
通讯作者：
Liu, Qingguang
影响因子：
56.9
作者：
Vasudevan, Shobha;Tong, Yingchun;Steitz, Joan A.
通讯作者：
Steitz, Joan A.