miR-370 modulates insulin receptor substrate-1 expression and inhibits the tumor phenotypes of oral carcinoma
miR-370 modulates insulin receptor substrate-1 expression and inhibits the tumor phenotypes of oral carcinoma
复制标题
DOI：
10.1111/odi.12046
复制
发表时间：
2013-09-01
期刊：
影响因子：
3.8
通讯作者：
Lin, S-C
中科院分区：
文献类型：
--
作者：
Chang, K-W;Chu, T-H;Lin, S-C
背景：microRNAs在肿瘤的发生中起着重要的作用。初步筛查研究表明，miR-370在口腔鳞癌(OSCC)组织中表达下调。胰岛素受体底物-1(IRS-1)是胰岛素样生长因子受体(IGFR)的底物，在恶性肿瘤中调节AKT/mTOR的激活。MiR-370与IRS-1之间的关系及其在口腔鳞癌发病机制中的作用尚不清楚。利用稳定亚克隆和瞬时表达建立了miR-370的外源表达，并利用这些克隆研究了miR-370‘S在口腔鳞癌细胞中的功能。结果有神经侵袭的鳞癌组织中miR-370和IRS-1的表达低于对照口腔鳞癌组织。口腔鳞癌细胞miR-370的表达也低于正常口腔角质形成细胞，5-氮杂-2-脱氧胞苷可逆转这一现象。外源性miR-370的表达降低了口腔鳞癌细胞的迁移和贴壁非依赖性生长，这意味着miR-370具有抑制作用。抑制IRS-1的表达可降低miR-370对口腔鳞癌细胞贴壁非依赖性生长的促进作用。结论miR-370可以靶向IRS-1在口腔肿瘤发生中的作用。
Background MicroRNAs play important roles in carcinogenesis. A preliminary screening study suggested that down-regulation of miR-370 occurs in oral squamous cell carcinoma (OSCC) tissue. Insulin receptor substratre-1 (IRS-1) is the substrate of insulin-like growth factor receptor (IGFR), which modulates AKT/mTOR activation in malignancies. The relationship between miR-370 and IRS-1, and their functional roles in OSCC pathogenesis are unclear.Materials and Methods Primary OSCC specimens were examined for miR-370 expression. Exogenous expression of miR-370 was established using both stable subclones and transient expression, and these were used to gain insights into miR-370's functions in OSCC cells. Knockdown of miR-370 and IRS-1 was also carried out in OSCC cells using a small interference oligonucleotide approach.Results Squamous cell carcinoma tissues with perineural invasion had lowered miR-370 expression compared with contrasting OSCC. OSCC cells also exhibited lower miR-370 expression than normal oral keratinocytes, and this can be reversed by treatment with 5-aza-2-deoxycytidine. Exogenous miR-370 expression decreases the migration and anchorage-independent growth of OSCC cells, which implies a suppressor role for miR-370. The enhancement of anchorage-independent growth of OSCC cells through miR-370 inhibiting can be reduced by knockdown of IRS-1 expression.Conclusion This study concludes that miR-370 is able to target IRS-1 for oral tumorigenesis.