title: Inhibitory effects of Arhgap6 on cervical carcinoma cells.
abstract: Ras homology GTPase activation protein 6 (Arhgap6), as a member of the rhoGAP family of proteins, performs vital functions on the regulation of actin polymerization at the plasma membrane during several cellular processes. The role of Arhgap6 in the progression and development of cancer remains nearly unknown. This study aimed at exploring the effects of Arhgap6 on cervical carcinoma. Human cervical cancer cells HeLa and SiHa were transduced with a lentivirus targeting Arhgap6 (Arhgap6+), while CaSki and C4-1 cells were transfected with miRNA. Cell proliferation was identified by Cell Counting Kit-8 (CCK-8). Cell cycle distribution and cell apoptosis were identified by flow cytometry. The capacity of cell migration, invasion, and adhesion were detected by Transwell assay. Further, quantitative real-time PCR (qRT-PCR) and western blot were used to analyze the expression levels of Arhgap6 and several tumor-related genes. Co-immunoprecipitation assay was performed to validate the interaction between Arhgap6 and Rac3 (Ras-related C3 botulinum toxin substrate 3). Results showed that Arhgap6 inhibited cell proliferation, migration, invasion, and adhesion of cervical carcinoma, induced cell apoptosis, and caused cell cycle arrest in the G0/G1 phase (n = 3, p < 0.05). Expression of the tumor suppressor genes and oncogenes were up- and down-regulated respectively by Arhgap6, and Rac3 was proved to be the target of Arhgap6. Besides, in in vivo assays, tumor size and weight were destructed in Arhgap6+ athymic nude mouse. This study indicated that Arhgap6 may play a role in the treatment of cervical cancer as a tumor supressor.
authors.affiliation: Department of Gynecology and Obstetrics, Huashan Hospital North, Fudan University, Shanghai, 200040, People's Republic of China.
authors.forename: Junping
authors.initials: J
authors.lastname: Li
authors.affiliation: Institute of Antibiotics,Huashan Hospital, Fudan University, Shanghai, 200040, People's Republic of China. liuyang@fudan.edu.cn.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, 200040, People's Republic of China. yinyihua@51mch.com.
authors.forename: Yihua
authors.initials: Y
authors.lastname: Yin
mesh_terms: D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D005260:Female; D005434:Flow Cytometry; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D064593:Heterografts; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000473:pathology; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection; D002583:Uterine Cervical Neoplasms / Q000378:metabolism / Q000473:pathology*
chemical_list: C109971:ARHGAP6 protein, human; D020690:GTPase-Activating Proteins; D034741:RNA, Small Interfering
keywords: Arhgap6; Cell proliferation; Cervical carcinoma; Metastasis; Signaling pathway