Liao Aijun, Tan Gao, Chen Lin, Zhou Weiwei, Hu Hongsai
Department of Gastroenterology, The First Affiliated Hospital of South China University, Hengyang, Hunan Province, China.
Gastric Cancer Research Center of Hunan Province, Hunan, China.
Oncotarget. 2016 Feb 2;7(5):5842-51. doi: 10.18632/oncotarget.6813.
Although interaction with DNA repair proteins has demonstrated that RASSF1A is a tumour suppressor gene, much attention has been directed in recent years towards its roles in regulating the cell cycle. However, the precise mechanism remains unclear. Uncovering how RASSF1A participates in regulating the cell cycle is critical to exploring effective therapeutic targets for gastric cancer. Here we show that RASSF1A could regulate 14 miRNAs' expression in the typical human gastric cancer line SGC-7901, of which miR-711 was upregulated the most. Moreover, for SGC-7901 cells, miR-711 was found to downregulate CDK4 expression, and to arrest the cell cycle in the G1 phase. Our results suggest that RASSF1A inhibits the proliferation of gastric cancer cells by upregulating the expression of miR-711, which arrested gastric cancer cells in the G1 phase by downregulating expression of CDK4. This finding might provide us with a novel therapeutic target for gastric cancer by increasing RASSF1A expression via miR-711 regulation.
尽管与DNA修复蛋白的相互作用已表明RASSF1A是一种肿瘤抑制基因,但近年来人们对其在调节细胞周期中的作用给予了极大关注。然而,确切机制仍不清楚。揭示RASSF1A如何参与调节细胞周期对于探索胃癌的有效治疗靶点至关重要。在此我们表明,RASSF1A可调节典型人胃癌细胞系SGC - 7901中14种miRNA的表达,其中miR - 711上调最为明显。此外,对于SGC - 7901细胞,发现miR - 711可下调CDK4表达,并使细胞周期停滞在G1期。我们的结果表明,RASSF1A通过上调miR - 711的表达来抑制胃癌细胞增殖,而miR - 711通过下调CDK4表达使胃癌细胞停滞在G1期。这一发现可能通过调控miR - 711增加RASSF1A表达,为我们提供一种新的胃癌治疗靶点。