Department of Hepatobiliary Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250014, Shandong Province, China.
Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250014, Shandong Province, China.
Biomed Pharmacother. 2016 Oct;83:792-797. doi: 10.1016/j.biopha.2016.07.037. Epub 2016 Aug 2.
microRNA (miRNA) plays critical role in HCC initiation and development, many miRNAs have been reported to regulate HCC progression. In this study, we studied the role of miR-1299 in cell proliferation of HCC. We found miR-1299 was significantly downregulated in HCC cells and tissues. miR-1299 overexpression inhibited cell proliferation and arrested cell cycle in G0/G1 phase analyzed by MTT assay, soft agar assay, BrdU cell proliferation assay and cell cycle assay, while miR-1299 knockdown promoted cell proliferation and accelerated G1/S transition. Further analysis suggested the key regulator of G1/S transition, cyclin-dependent kinase 6 (CDK6) was the target of miR-1299, miR-1299 inhibited CDK6 expression and bound to the 3'UTR of CDK6. When double knockdown of miR-1299 and CDK6 promoted cell proliferation copied the phenotype caused by miR-1299 overexpression, suggesting miR-1299 inhibits cell proliferation by targeting CDK6. In summary, our data revealed miR-1299 inhibits cell proliferation, and might be a target for HCC therapy.
microRNA (miRNA) 在 HCC 的发生和发展中起着关键作用,许多 miRNA 已被报道能调节 HCC 的进展。在本研究中,我们研究了 miR-1299 在 HCC 细胞增殖中的作用。我们发现 miR-1299 在 HCC 细胞和组织中显著下调。MTT 检测、软琼脂检测、BrdU 细胞增殖检测和细胞周期检测表明,miR-1299 过表达抑制细胞增殖并将细胞周期阻滞在 G0/G1 期,而 miR-1299 敲低则促进细胞增殖并加速 G1/S 期转变。进一步的分析表明,G1/S 期的关键调节因子细胞周期蛋白依赖性激酶 6(CDK6)是 miR-1299 的靶标,miR-1299 抑制 CDK6 的表达并与 CDK6 的 3'UTR 结合。当 miR-1299 和 CDK6 的双重敲低促进细胞增殖复制了 miR-1299 过表达引起的表型时,表明 miR-1299 通过靶向 CDK6 抑制细胞增殖。总之,我们的数据揭示了 miR-1299 抑制细胞增殖,可能是 HCC 治疗的一个靶点。