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循环微RNA-21通过靶向RASA1参与宫颈癌的淋巴结转移。

Circulating MicroRNA-21 Is Involved in Lymph Node Metastasis in Cervical Cancer by Targeting RASA1.

作者信息

Zhang Lingyun, Zhan Xin, Yan Dingding, Wang Zhihua

机构信息

*Department of Obstetrics and Gynecology, Hangzhou First People's Hospital; and †Department of Gynecology Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China.

出版信息

Int J Gynecol Cancer. 2016 Jun;26(5):810-6. doi: 10.1097/IGC.0000000000000694.

Abstract

The aims of this study were to discover if increased circulating microRNA-21 (miR-21) expression in serum is associated with lymph node metastasis in patients with cervical cancer and look further into the molecular mechanism of these. Whole-blood samples from 89 patients who have been histopathologically confirmed as having cervical cancer and 20 control subjects were collected, and then the association between lymph node metastasis and the level of circulating miR-21 was compared. Then cervical cancer cell lines HeLa (HPV-18 DNA, E6/E7RNA) and HT-3 (HPV DNA, E6/E7RNA) were used to confirm the interaction between miR-21 and RASA1. The role of RASA1 in cervical cancer cell migration was also studied in HeLa. Increased circulating miR-21 expression in serum is associated with lymph node metastasis in patients with cervical cancer. MicroRNA-21 reduces RASA1 expression in cervical cancer cell lines and promotes cervical cancer cell migration via RASA1. Furthermore, Ras-induced epithelial-mesenchymal transition contributes to miR-21/RASA1 axis promoting cervical cancer cell migration. Circulating miR-21 in serum could be a promising biomarker in auxiliary diagnosis of lymph node metastasis in cervical cancer, and inhibition of miR-21/RASA1 axis could be a possible strategy to restrain migration of cervical cancer.

摘要

本研究的目的是探究血清中循环微RNA-21(miR-21)表达增加是否与宫颈癌患者的淋巴结转移相关,并进一步深入研究其分子机制。收集了89例经组织病理学确诊为宫颈癌的患者及20例对照者的全血样本,随后比较淋巴结转移与循环miR-21水平之间的关联。接着,使用宫颈癌细胞系HeLa(HPV-18 DNA,E6/E7RNA)和HT-3(HPV DNA,E6/E7RNA)来证实miR-21与RASA1之间的相互作用。还在HeLa细胞中研究了RASA1在宫颈癌细胞迁移中的作用。血清中循环miR-21表达增加与宫颈癌患者的淋巴结转移相关。微RNA-21降低宫颈癌细胞系中RASA1的表达,并通过RASA促进宫颈癌细胞迁移。此外,Ras诱导的上皮-间质转化有助于miR-21/RASA1轴促进宫颈癌细胞迁移。血清中循环miR-21可能是宫颈癌淋巴结转移辅助诊断中有前景的生物标志物,抑制miR-21/RASA1轴可能是抑制宫颈癌细胞迁移的一种可行策略。

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