Ectopic expression of MiR-125a inhibits the proliferation and metastasis of hepatocellular carcinoma by targeting MMP11 and VEGF.
Ectopic expression of MiR-125a inhibits the proliferation and metastasis of hepatocellular carcinoma by targeting MMP11 and VEGF.
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MiR-125a异位表达通过靶向MMP11和VEGF抑制肝细胞癌的增殖和转移
DOI：
10.1371/journal.pone.0040169
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Fan D
中科院分区：
文献类型：
--
作者：
Bi Q;Tang S;Xia L;Du R;Fan R;Gao L;Jin J;Liang S;Chen Z;Xu G;Nie Y;Wu K;Liu J;Shi Y;Ding J;Fan D
背景研究表明，miR-125 a在肝癌发生中起重要作用，但miR-125 a在肝细胞癌（HCC）中的作用尚不清楚。方法学/主要的真实的时间-PCR（qRT-PCR）用于测试miR-125 a在HCC中的显著性。通过miR-125 a的异位表达检测miR-125 a对肝癌细胞体外和体内增殖和转移的影响。通过双荧光素酶报告、qRT-PCR和蛋白质印迹（WB）分析确定miR-125 a的预测靶基因。采用免疫组化（IHC）法检测靶基因的表达，并分析miR-125 a与其靶基因的相关性及预后价值。在HCC组织和细胞系中均观察到miR-125 a降低，并且与患者的侵袭性病理特征相关。上调miR-125 a可通过抑制基质金属蛋白酶11（MMP 11）和血管内皮生长因子A（VEGF-A）的表达，抑制肿瘤细胞的恶性表型。此外，在HCC组织中，miR-125 a表达与MMP 11和VEGF-A表达均呈负相关。抑制miR-125 a可以增加MMP 11和VEGF-A的表达，并且靶向MMP 11或VEGF-A mRNA的RNA干扰可以挽救miR-125 a功能的丧失。miR-125 a通过靶向MMP 11和VEGF-A抑制HCC的增殖和转移。miR-125 a的上调可能是一种有前途的方法和HCC的预后标志物。
Background Studies have been shown that miR-125a plays an important role in carcinogenesis, however, the role of miR-125a in hepatocellular carcinoma (HCC) remains elusive. Methodology/Principal Real time-PCR (qRT-PCR) was performed to test the significance of miR-125a in HCC. Ectopic expression of miR-125a was used to test the influences of miR-125a on proliferation and metastasis of HCC cells in vitro and in vivo. Predicted target genes of miR-125a were determined by dual-luciferase reporting, qRT-PCR, and western blot (WB) analyses. Then immunohistochemical staining (IHC) was used to detect the expression of target genes, and the correlations and prognostic values of miR-125a and its target genes were also investigated. Conclusions/Significance Decreased miR-125a was observed in both HCC tissues and cell lines, and associated with patients’ aggressive pathologic features. Up-regulating miR-125a significantly inhibited the malignant phenotypes by repressing the expression of matrix metalloproteinase 11 (MMP11) and vascular endothelial growth factor A (VEGF-A) both in vitro and in vivo. Furthermore, miR-125a expression was inversely correlated with both MMP11 and VEGF-A expression in HCC tissues. Inhibiting miR-125a could increase both MMP11 and VEGF-A expression, and RNA interference targeting MMP11 or VEGF-A mRNA could rescue the loss of miR-125a functions. MiR-125a inhibits the proliferation and metastasis of HCC by targeting MMP11 and VEGF-A. Up-regulation of miR-125a might be a promising approach and a prognostic marker for HCC.
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