微小RNA-34a通过靶向E2F3并调节生存素抑制人乳头瘤病毒阳性宫颈癌细胞的活力和侵袭能力。

MiR-34a Inhibits Viability and Invasion of Human Papillomavirus-Positive Cervical Cancer Cells by Targeting E2F3 and Regulating Survivin.

作者信息

Geng Dianzhong, Song Xiaohua, Ning Fangling, Song Qianhua, Yin Honghua

机构信息

*Department of Oncology, Binzhou Medical University Hospital; †Department of Obstetrics and Gynecology, Binzhou People's Hospital; and ‡Department of Obstetrics and Gynecology, Zouping Maternal and Child Health-Care Hospital, Shandong, China.

出版信息

Int J Gynecol Cancer. 2015 May;25(4):707-13. doi: 10.1097/IGC.0000000000000399.

DOI:10.1097/IGC.0000000000000399

PMID:25675046

Abstract

OBJECTIVE

Previous studies confirmed that high-risk human papillomavirus (HR-HPV) infection is a risk factor of cervical cancer, and the infection was associated with significantly reduced miR-34a expression during carcinogenesis. However, the downstream targets of miR-34a and their roles are still not well understood. This study explored the regulative role of miR-34a on E2F3 and survivin expression and the viability and invasion of HPV-positive cervical cancer cells.

METHODS

MiR-34a and survivin expression in 56 cases of HR-HPV-positive patients, 28 cases of HR-HPV-negative patients, and 28 normal cases without HR-HPV infections were measured. Human papillomavirus-18-positive HeLa cervical cancer cells and HPV-16-positive SiHa cells were used to explore the effect of miR-34a on cell viability and invasion. The molecular target of miR-34a was also explored in cervical cancer cells.

RESULTS

The results showed that miR-34a overexpression could inhibit HPV-positive cancer cell viability, whereas its downregulation promoted cell viability. E2F3 is a direct target of miR-34a in HPV-positive cervical cancer cells. By targeting E2F3, miR-34a could regulate the expression of survivin. Thus, through regulating E2F3 and survivin, miR-34a could reduce the viability and invasion of HPV-positive cervical cancer cells.

CONCLUSIONS

This study confirmed a novel miR-34a-E2F3-survivin axis in the tumor suppressor role of miR-34a in cervical cancer.

摘要

目的

既往研究证实，高危型人乳头瘤病毒（HR-HPV）感染是宫颈癌的一个危险因素，且该感染与致癌过程中miR-34a表达显著降低有关。然而，miR-34a的下游靶点及其作用仍未完全明确。本研究探讨了miR-34a对E2F3和survivin表达以及HPV阳性宫颈癌细胞活力和侵袭的调节作用。

方法

检测了56例HR-HPV阳性患者、28例HR-HPV阴性患者以及28例无HR-HPV感染的正常对照者中miR-34a和survivin的表达。采用人乳头瘤病毒18型阳性的HeLa宫颈癌细胞和HPV-16阳性的SiHa细胞，探讨miR-34a对细胞活力和侵袭的影响。同时在宫颈癌细胞中探索miR-34a的分子靶点。

结果

结果显示，miR-34a过表达可抑制HPV阳性癌细胞的活力，而其表达下调则促进细胞活力。E2F3是HPV阳性宫颈癌细胞中miR-34a的直接靶点。通过靶向E2F3，miR-34a可调节survivin的表达。因此，通过调节E2F3和survivin，miR-34a可降低HPV阳性宫颈癌细胞的活力和侵袭能力。