BRIP1 inhibits the tumorigenic properties of cervical cancer by regulating RhoA GTPase activity

BRIP1 通过调节 RhoA GTPase 活性抑制宫颈癌的致瘤特性

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作者:Wei Zou, Xiangdong Ma, Wei Hua, Biliang Chen, Yanhong Huang, Detang Wang, Guoqing Cai

Abstract

Breast cancer 1, early onset (BRCA1)-interacting protein 1 (BRIP1), a DNA-dependent adenosine triphosphatase and DNA helicase, is required for BRCA-associated DNA damage repair functions, and may be associated with the tumorigenesis and aggressiveness of various cancers. The present study investigated the expression of BRIP1 in normal cervix tissues and cervical carcinoma via reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry assays. BRIP1 expression was observed to be reduced in squamous cancer tissue and adenocarcinoma compared with normal cervix tissue, and there were significant correlations between the reduction in BRIP1 expression and unfavorable variables, including the International Federation of Gynecologists and Obstetricians stage and presence of lymph node metastases. In order to elucidate the role of BRIP1 in cervical cancer, a BRIP1 recombinant plasmid was constructed and overexpressed in a cervical cancer cell line (HeLa). The ectopic expression of BRIP1 markedly inhibited the tumorigenic properties of HeLa cells in vitro, as demonstrated by decreased cell growth, invasion and adhesion, and increased cell apoptosis. In addition, it was identified that the inhibitory tumorigenic properties of BRIP1 may be partly attributed to the attenuation of RhoA GTPase activity. The present study provides a novel insight into the essential role of BRIP1 in cervical cancer, and suggests that BRIP1 may be a useful therapeutic target for the treatment of this common malignancy.

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