Liu Xiaorui, Li Jingjing, Yu Zujiang, Li Juan, Sun Ranran, Kan Quancheng
Oncol Res. 2017 Mar 13;25(3):427-435. doi: 10.3727/096504016X14747300207374. Epub 2016 Sep 30.
Hepatocellular carcinoma (HCC) is the most common cancer in the world. MicroRNAs (miRNAs) are a type of small noncoding RNA that can regulate the expression of target genes under physiological and pathophysiological conditions. Aberrant expression of microRNA-935 (miR-935) has been reported in cancer studies. However, its expression and mechanism in HCC remain unclear. In our study, we found that miR-935 was upregulated in liver cancer tissues and cells. Overexpression of miR-935 in liver cells promoted cell proliferation, tumorigenesis, and cell cycle progression, whereas inhibition of miR-935 reduced cell proliferation, tumorigenicity, and cell cycle progression. These changes in the properties of HCC cells were associated with upregulation of two well-known cellular G1/S transitional regulators: cyclin D1 and c-Myc. Additionally, we identified SOX7 as a direct target of miR-935. Overexpression of miR-935 inhibited SOX7 expression but promoted the levels of c-Myc and cyclin D1, which promotes cell proliferation and tumorigenesis; knockdown of miR-935 increased SOX7 level and inhibited c-Myc and cyclin D1 expression, whereas SOX7 silencing could promote cell proliferation, cell motility, and invasiveness in vitro. Our findings suggest that miR-935 represents a biomarker and a potential new target in HCC progression by suppressing SOX7 expression.
肝细胞癌(HCC)是全球最常见的癌症。微小RNA(miRNA)是一类小的非编码RNA,可在生理和病理生理条件下调节靶基因的表达。在癌症研究中已报道微小RNA-935(miR-935)表达异常。然而,其在HCC中的表达及机制仍不清楚。在我们的研究中,我们发现miR-935在肝癌组织和细胞中上调。肝细胞中miR-935的过表达促进细胞增殖、肿瘤发生和细胞周期进程,而抑制miR-935则降低细胞增殖、致瘤性和细胞周期进程。HCC细胞这些特性的变化与两种著名的细胞G1/S转换调节因子:细胞周期蛋白D1和c-Myc的上调有关。此外,我们确定SOX7是miR-935的直接靶标。miR-935的过表达抑制SOX7表达,但促进c-Myc和细胞周期蛋白D1的水平,从而促进细胞增殖和肿瘤发生;敲低miR-935可增加SOX7水平并抑制c-Myc和细胞周期蛋白D1表达,而沉默SOX7可促进体外细胞增殖、细胞运动和侵袭。我们的研究结果表明,miR-935通过抑制SOX7表达,代表了HCC进展中的一种生物标志物和潜在的新靶点。