MicroRNA-424 inhibits Akt3/E2F3 axis and tumor growth in hepatocellular carcinoma.
MicroRNA-424 inhibits Akt3/E2F3 axis and tumor growth in hepatocellular carcinoma.
复制标题
MicroRNA-424 抑制 Akt3/E2F3 轴和肝细胞癌中的肿瘤生长。
DOI：
10.18632/oncotarget.4811
复制
发表时间：
2015-09-29
期刊：
影响因子：
--
通讯作者：
Yang LY
中科院分区：
文献类型：
--
作者：
Yang H;Zheng W;Shuai X;Chang RM;Yu L;Fang F;Yang LY
通过比较miRNAs在不同亚型肝癌中的表达谱，我们确定miR-424是一个与肝癌相关的miRNA。我们发现miR-424在肝癌组织和6种肝癌细胞系中的表达显著降低。显著地，其表达水平与肿瘤大小、多发结节、静脉侵犯、TNM分期和总生存期有关。我们发现，上调的miR-424在体内和体外都能抑制肝癌细胞的增殖。多途径报告阵列显示miR-424抑制了pRb-E2F途径。AKT3和E2F3一直被认为是miR-424的靶点，异位miR-424的表达抑制了AKT3和E2F3的表达。通过siRNA沉默AKT3和E2F3，复制了异位miR-424对肝癌生长的影响。而AKT3和E2F3的过表达减弱了miR-424对肝癌生长的影响。总之，我们的数据表明miR-424在肝癌的发生和发展中具有肿瘤抑制作用，具有治疗意义。MiR-424的表达与肝细胞癌患者的生存密切相关，提示miR-424可能是判断肝细胞癌预后的有价值的生物标志物。
By comparing the expression profiles of miRNAs in different subtypes of HCC, we identified miR-424 as a HCC related miRNA. We found that the expression of miR-424 was significantly decreased in HCC tissues and six liver cancer cell lines. Significantly, its expression levels were correlated with tumor size, multiple nodules, vein invasion, TNM stage and overall survival of HCC. We showed that up-regulated miR-424 suppressed HCC cell proliferation in vivo and in vitro. Multi-pathway reporter arrays suggested that miR-424 suppressed the pRb-E2F pathway. Consistently, Akt3 and E2F3 were identified as the targets of miR-424 as evidenced by that ectopic miR-424 expression suppressed Akt3 and E2F3 expressions. Silencing Akt3 and E2F3 by siRNA pheno-copied the effect of ectopic miR-424 on HCC growth. Whereas, overexpression of Akt3 and E2F3 attenuated the effect of miR-424 on HCC growth. Together, our data demonstrated a tumor suppressor role for miR-424 in HCC development and progression with therapeutic implications. The strong correlation of miR-424 expression with HCC patient survival suggests that miR-424 could be a valuable biomarker for HCC prognosis.