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.

Human Papillomavirus Modulates Matrix Metalloproteinases During Carcinogenesis: Clinical Significance and Role of Viral Oncoproteins

“…As observed for cervical cancer, MMP2, MMP9 MMP12 and MMP13 were increased in intraepithelial and invasive vulvar lesions compared with normal tissues (78)(79)(80)(81). In this type of cancer, up-regulation of MMP2 and MMP9 in vivo was found to be dependent on signaling via the Ras homologue gene family member A (82). Lovastatin downregulated RhoA, MMP2 and MMP9 expression, suggesting a potential therapeutic application against vulvar cancer.…”

Bioinformatics analysis of SRSF1‑controlled gene networks in colorectal cancer

“…Genes that regulate apoptosis, including HSP90AA1, RHOA, PTEN and RPS6KB1, were highly associated with the expression level of SRSF1. RHOA is a member of Rho GTPases, which are involved in major aspects of cancer development, including cell proliferation, apoptosis, cell polarity, adhesion, migration and invasion ( 37 ). Overexpression of RHOA is associated with invasion and poor prognosis in colorectal cancer ( 38 ).…”

Discovery of Cellular RhoA Functions by the Integrated Application of Gene Set Enrichment Analysis

“…RhoA is related to various pathological con-ditions (Narumiya and Thumkeo, 2018). RhoA and RhoC are upregulated or engaged in various tumors, including gastric cancer, testicular cancer, squamous cell carcinoma, hepatocellular carcinoma, and pancreatic adenocarcinoma (Suwa et al, 1998;Clark et al, 2000;Simpson et al, 2004;Faried et al, 2006;Wang et al, 2007;Porter et al, 2016;Wang et al, 2016). Recent reports have identified mutated RhoA in several tumors, such as diffuse gastric cancer and angioimmunoblastic T cell lymphoma (Kakiuchi et al, 2014;Sakata-Yanagimoto et al, 2014;Wang et al, 2014;Yoo et al, 2014;Zhou et al, 2014;Zhao et al, 2015).…”