MicroRNA-497 is a potential prognostic marker in human cervical cancer and functions as a tumor suppressor by targeting the insulin-like growth factor 1 receptor-猫眼课题宝

DOI：

10.1016/j.surg.2012.12.004

发表时间：

2013-06-01

期刊：

SURGERY

影响因子：

3.8

通讯作者：

中科院分区：

医学2区

文献类型：

作者：

Luo, Min;Shen, Dongxiang;Wang, Wei

背景。越来越多的证据表明，microRNA在人类恶性肿瘤中发挥癌基因或抑癌基因的作用，但microRNA（miR）-497在人宫颈癌中的作用仍不清楚。我们的目的是分析miR497在人宫颈癌中的临床病理和预后意义，并研究miR-497对宫颈癌细胞恶性表型的影响。方法。首先，我们检测了 HPV-16 永生化宫颈上皮细胞系和其他 4 种宫颈癌细胞系（HeLa、Caski、SiHa 和 HeLa-S3）中的 miR-497 表达。然后分析宫颈癌组织和配对非肿瘤组织中miR497的表达，并分析其与临床病理特征和生存的相关性。最后进一步研究miR-497在肿瘤增殖、凋亡、迁移、侵袭和靶基因表达等调控中的作用。与 HPV-16 永生化宫颈上皮细胞系或配对的非肿瘤组织相比，miR-497 在宫颈癌细胞或组织中表达下调。此外，miR-497的下降与国际妇产科联合会的分期标准和宫颈癌患者的淋巴结转移密切相关。多变量 Cox 分析显示 miR-497 低表达似乎是不利的预后因素。 miR497 的瞬时强制表达通过诱导 Caspase-3 依赖性细胞凋亡来降低 HeLa 和 SiHa 细胞的生长和集落形成能力。 miR-497的强制表达抑制了宫颈癌细胞的迁移和侵袭。通过计算 miRNA 靶标预测和功能分析，证明 miR-497 与 IGF-1R mRNA 的 3' 非翻译区结合，并且 miR-497 的上调会下调 IGF-1R 蛋白的表达。进一步研究表明，小干扰RNA介导的IGF-1R敲低可以模拟miR-497强制表达对宫颈癌细胞恶性表型的影响。结论。 MiR-497 可能是一种潜在的预后标志物，并通过转录后靶向 IGF-1R 作为人类宫颈癌的肿瘤抑制因子

Background. Increasing evidence has shown that microRNAs function as oncogenes or tumor suppressors in human malignancies, but the roles of microRNA (miR)-497 in human cervical cancer still remain unclear Our aim was to analyze the clinicopathologic and prognostic significance of miR497 in human cervical cancer and to investigate the effects of miR-497 on the malignant phenotype of cervical cancer cells.Methods. First, we detected miR-497 expression in the HPV-16-immortalized cervical epithelial cell lines and 4 other cervical,cancer cell lines (HeLa, Caski, SiHa, and HeLa-S3). Then the expression of miR497 was analyzed in cervical cancer tissues and paired nontumor tissues, and its correlation with clinicapathologic features and survival was analyzed. Finally, the roles of miR-497 in regulation of tumor proliferation, apoptosis, migration, invasion, and target gene expression were further investigated.Results. MiR-497 was downregulated in cervical cancer cells or tissues compared with HPV-16-immortalized cervical epithelial cell lines or the paired nontumor tissues. Also, the decrease in miR-497 correlated closely with the criteria of the International Federation of Gynaecolo gy and Obstetrics stage and lymph node.metastases in patients with cervical cancer. Multivariate Cox analysis showed that low miR-497 expression appeared to be an unfavorable prognostic factor. Transient forced expression of miR497 decreased the growth and colony-formation capacity of HeLa and SiHa cells by inducing Caspase-3-dependent apoptosis. Forced expression of miR-497 suppressed the migration and invasiveness of cervical cancer cells. By computational miRNA target prediction and functional analysis, miR-497 was demonstrated to bind to the 3' untranslated regions of IGF-1R mRNA, and upregulation of miR-497 downregulated IGF-1R protein expression. Further investigation showed that small interfering RNAmediated IGF-1R knockdown could mimic the effect of enforced miR-497 expression on the malignant phenotypes of cervical cancer cells.Conclusion. MiR-497 may be a potential prognostic marker and functions as a tumor suppressor in human cervical cancer by post-transcriptionally targeting IGF-1R

MicroRNA-497 is a potential prognostic marker in human cervical cancer and functions as a tumor suppressor by targeting the insulin-like growth factor 1 receptor

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