Department of Surgery of Ruijin Hospital, Shanghai Key Laboratory for Gastric Neoplasia, Affiliated to Shanghai Jiao Tong University, School of Medicine, Ruijin er Road, No. 197, 200025, Shanghai, China.
Anticancer Agents Med Chem. 2013 Feb;13(2):270-5. doi: 10.2174/1871520611313020013.
MicroRNAs (miRNAs) and promoter hypermethylation are vital epigenetic mechanisms for transcriptional inactivation of tumor suppressor. IRX1 is a newly identified tumor suppressor gene and hypermethylation involves the decreased expression in gastric cancer. However, the microRNA regulatory mechanism on IRX1 expression is still unclear. In this study, we report an IRX1-targeting miRNA-544, which directly targets 3'-UTR of IRX1 gene by luciferase reporter assay. miR-544 suppresses the protein expression of IRX1 gene by Western blot and immunocytochemistry. Ectopic expression of miR-544 promotes cell proliferation and cell cycle progression significantly in vitro on gastric cancer cells. The study suggests that miR-544 is an oncogenic microRNA in gastric cancer. Over expression of miR-544 contributes to the inactivation and low-expression of IRX1 in gastric cancer. These findings are helpful for clarifying the molecular mechanisms involved in gastric carcinogenesis and indicate that miR-544 is a key regulator in switching cell cycle on or off. miR-544 may be a potential molecular target in miRNA-based strategy on gastric cancer.
微小 RNA（miRNAs）和启动子甲基化是肿瘤抑制基因转录失活的重要表观遗传机制。IRX1 是一个新鉴定的肿瘤抑制基因，其甲基化涉及胃癌中表达的降低。然而，IRX1 表达的 microRNA 调节机制尚不清楚。在这项研究中，我们报告了一个靶向 IRX1 的 miRNA-544，它通过荧光素酶报告基因检测直接靶向 IRX1 基因的 3'UTR。miR-544 通过 Western blot 和免疫细胞化学抑制 IRX1 基因的蛋白表达。在体外，过表达 miR-544 可显著促进胃癌细胞的增殖和细胞周期进程。该研究表明，miR-544 是胃癌中的致癌 microRNA。miR-544 的过表达导致胃癌中 IRX1 的失活和低表达。这些发现有助于阐明胃癌发生过程中涉及的分子机制，并表明 miR-544 是开启或关闭细胞周期的关键调节因子。miR-544 可能是基于 miRNA 的胃癌治疗策略中的一个潜在分子靶点。
