Department of Gastroenterology, Minhang District Central Hospital, Shanghai, People's Republic of China.
Med Oncol. 2012 Jun;29(2):856-63. doi: 10.1007/s12032-011-9823-1. Epub 2011 Jan 25.
MicroRNAs (miRNAs) have emerged as post-transcriptional regulators that are critically involved in the pathogenesis of a number of human cancers. Recently, cyclin-dependent kinase 6 (CDK6) is found to be up-regulated in several types of human tumors and has been implicated in cancer initiation and progression. We have identified miR-107 as a potential regulator of CDK6 expression. A bioinformatics search revealed a putative target site for miR-107 within the CDK6 3' untranslated region. Expression of miR-107 in gastric cancer cell lines was found inversely correlated with CDK6 expression. miR-107 could significantly suppress CDK6 3' UTR luciferase reporter activity, and this effect was not detectable when the putative 3' UTR target site was mutated. Consistent with the results of the reporter assay, ectopic expression of miR-107 reduced both mRNA and protein expression levels of CDK6, inhibited proliferation, induced G1 cell cycle arrest, and blocked invasion of the gastric cancer cells. Our results suggest that miR-107 may have a tumor suppressor function by directly targeting CDK6 to inhibit the proliferation and invasion activities of gastric cancer cells.
微小 RNA（miRNAs）作为转录后调控因子，在许多人类癌症的发病机制中起着关键作用。最近，细胞周期蛋白依赖性激酶 6（CDK6）在几种类型的人类肿瘤中被发现上调，并被认为与癌症的发生和进展有关。我们已经确定 miR-107 是 CDK6 表达的潜在调节因子。生物信息学搜索显示，miR-107 在 CDK6 3'非翻译区存在一个假定的靶位点。在胃癌细胞系中，miR-107 的表达与 CDK6 的表达呈负相关。miR-107 可以显著抑制 CDK6 3'UTR 荧光素酶报告基因活性，而当假定的 3'UTR 靶位点发生突变时，则无法检测到这种作用。与报告基因检测结果一致，miR-107 的异位表达降低了 CDK6 的 mRNA 和蛋白表达水平，抑制了增殖，诱导了 G1 细胞周期停滞，并阻止了胃癌细胞的侵袭。我们的研究结果表明，miR-107 可能通过直接靶向 CDK6 抑制胃癌细胞的增殖和侵袭活性，从而发挥肿瘤抑制功能。
