title: The role of RhoA in vulvar squamous cell carcinoma: a carcinogenesis, progression, and target therapy marker.
abstract: Ras homologue gene family member A (RhoA) is involved in tumor mobility, invasion, and metastasis. We detected RhoA expression in vulvar squamous cell carcinoma (VSCC) tissue, measured RhoA expression in the VSCC cell phenotype, and measured the expression of the relevant molecules after RhoA small interfering RNA (siRNA) transfection in SW962 cells. RhoA has a higher expression level in VSCC than normal vulva skin tissue and was positively associated with the International Federation of Gynecology and Obstetrics (FIGO) stage and differentiation; besides, VSCC patients with lymph node metastasis had higher positive RhoA expression. RhoA messenger RNA and protein expression was significantly reduced in the RhoA siRNA transfectants as compared with the negative control (NC) and mock-transfected cells (p < 0.05). The RhoA siRNA transfectants lead to low growth, G1 arrest, high apoptosis, low migration and invasion (p < 0.05), and suppressed lamellipodia formation as compared to NC and mock-transfected cells. Besides, matrix metalloproteinase-2 (MMP2), MMP9, and cyclinA1 protein expression was downregulated, while that of Bax was upregulated in the RhoA siRNA transfectants (p < 0.05). SW962 cell proliferation rates were significantly lovastatin dose-dependent. Lovastatin caused G1 arrest, high apoptosis, low migration and invasion (p < 0.05), and suppression of lamellipodia formation. Similar to the RhoA siRNA transfectants, lovastatin treatment downregulated RhoA, MMP2, MMP9, and cyclinA1 protein expression, while upregulating that of Bax as compared to that of the NC (p < 0.05). Abnormal RhoA expression in vulvar carcinoma is involved in tumor proliferation and invasion and may be a treatment target. The RhoA inhibitor lovastatin alters VSCC cell migration and proliferation and may be effective for treating VSCC.
authors.affiliation: Department of Gynecology, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Gynecology, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Gynecology, Panjin Central Hospital, Panjin, 124010, China.
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Zhang
authors.affiliation: Department of Gynecology, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China.
authors.forename: Yun-Xia
authors.initials: YX
authors.lastname: Zhao
authors.affiliation: Department of Gynecology, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China. xinwu.1964@aliyun.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Wu
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000502:physiology*; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000473:pathology*; D045744:Cell Line, Tumor; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008148:Lovastatin / Q000494:pharmacology; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D014846:Vulvar Neoplasms / Q000209:etiology / Q000473:pathology*; D020742:rhoA GTP-Binding Protein / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology*
chemical_list: D014408:Biomarkers, Tumor; C066737:RHOA protein, human; D008148:Lovastatin; D020742:rhoA GTP-Binding Protein
keywords: Lovastatin; Progression; RhoA; Tumorigenesis; Vulvar squamous cell carcinoma