MicroRNA-497 是人类宫颈癌的一个潜在预后标志物，通过靶向胰岛素样生长因子 1 受体发挥肿瘤抑制作用。

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.

机构信息

Department of Obstetrics and Gynecology, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou, China.

出版信息

Surgery. 2013 Jun;153(6):836-47. doi: 10.1016/j.surg.2012.12.004. Epub 2013 Feb 28.

DOI:10.1016/j.surg.2012.12.004

PMID:23453369

Abstract

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 miR-497 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 miR-497 was analyzed in cervical cancer tissues and paired nontumor tissues, and its correlation with clinicopathologic 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 Gynaecology 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 miR-497 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 RNA-mediated 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.

摘要

背景

越来越多的证据表明，microRNAs 在人类恶性肿瘤中作为癌基因或肿瘤抑制因子发挥作用，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 miR-497 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另外 4 种宫颈癌细胞系（HeLa、Caski、SiHa 和 HeLa-S3）中 miR-497 的表达。然后分析了宫颈癌组织和配对非肿瘤组织中 miR-497 的表达，并分析其与临床病理特征和生存的关系。最后，进一步研究了 miR-497 在调节肿瘤增殖、凋亡、迁移、侵袭和靶基因表达中的作用。

结果

与 HPV-16 永生化宫颈上皮细胞系或配对非肿瘤组织相比，miR-497 在宫颈癌细胞或组织中下调。此外，miR-497 的减少与宫颈癌患者的国际妇产科联合会分期和淋巴结转移标准密切相关。多变量 Cox 分析显示，低 miR-497 表达似乎是预后不良的因素。瞬时强制表达 miR-497 通过诱导 Caspase-3 依赖性凋亡，降低 HeLa 和 SiHa 细胞的生长和集落形成能力。强制表达 miR-497 抑制宫颈癌细胞的迁移和侵袭。通过计算 miRNA 靶预测和功能分析，miR-497 被证明与 IGF-1R mRNA 的 3'非翻译区结合，上调 miR-497 下调 IGF-1R 蛋白表达。进一步的研究表明，小干扰 RNA 介导的 IGF-1R 敲低可以模拟强制表达 miR-497 对宫颈癌细胞恶性表型的影响。