Department of Pathology, School of Medicine, Shandong University, Jinan, PR China.
Exp Mol Pathol. 2013 Aug;95(1):91-7. doi: 10.1016/j.yexmp.2013.05.003. Epub 2013 May 25.
MicroRNAs play important roles in the processes of tumor initiation and progression. The expression level of miR-145 in gastric, liver, and cervical cancers has been rarely investigated. Whether miR-145 may function as a common tumor suppressor in the generation of tumor phenotype needs to be clarified. miR-145 expression was determined by RT-qPCR in various human cancer tissues including those of gastric, liver, colon, and cervical cancers. Cancer cell lines were transfected with miR-145 precursor, anti-miR-145 inhibitor, or negative control, and cells' proliferation, migration, and invasion activities were analyzed. The gene target of miR-145 was confirmed by luciferase assay and Western blot. The miR-145 expression level was lower by 37.68-, 2.64-, 2.69- and 2.39-fold in gastric, liver, colon, and cervical cancer tissues, respectively, compared to corresponding nontumorous controls. Moreover, miR-145 levels were significantly downregulated in various cancer cell lines. We further demonstrated that miR-145 could suppress anchorage-independent growth and cell motility in both the liver cancer cell line Hep-G2 and the gastric cancer cell line MKN-45, and inhibited cell proliferation in a cell type-specific manner. Insulin receptor substrate-1 (IRS1) was identified as a target gene of miR-145, by which miR-145 was able to suppress cell proliferation. miR-145 suppresses cell proliferation, anchorage-independent growth, cell motility, and may serve as a tumor suppressor.
微小 RNA 在肿瘤发生和发展过程中发挥重要作用。miR-145 在胃癌、肝癌和宫颈癌中的表达水平鲜有研究。miR-145 是否可能作为一种常见的肿瘤抑制因子在肿瘤表型的产生中发挥作用,需要进一步阐明。采用 RT-qPCR 法检测了各种人类癌组织(包括胃癌、肝癌、结肠癌和宫颈癌组织)中 miR-145 的表达。用 miR-145 前体、抗 miR-145 抑制剂或阴性对照转染癌细胞系,分析细胞的增殖、迁移和侵袭活性。通过荧光素酶报告基因检测和 Western blot 验证 miR-145 的基因靶标。与相应的非肿瘤对照相比,胃癌、肝癌、结肠癌和宫颈癌组织中 miR-145 的表达水平分别降低了 37.68、2.64、2.69 和 2.39 倍。此外,miR-145 在各种癌细胞系中也显著下调。我们进一步证明,miR-145 可以抑制肝癌细胞系 Hep-G2 和胃癌细胞系 MKN-45 的锚定非依赖性生长和细胞迁移,并以细胞类型特异性方式抑制细胞增殖。胰岛素受体底物-1(IRS1)被鉴定为 miR-145 的靶基因,miR-145 可以通过该基因抑制细胞增殖。miR-145 抑制细胞增殖、锚定非依赖性生长、细胞迁移,可能作为肿瘤抑制因子发挥作用。