title: Silencing RhoA inhibits migration and invasion through Wnt/β-catenin pathway and growth through cell cycle regulation in human tongue cancer.
abstract: Ras homolog gene family member A (RhoA) has been identified as a critical regulator of tumor aggressive behavior. In this study, we assessed the role of RhoA in the mechanisms underlying growth, migration, and invasion of squamous cell carcinoma of tongue (TSCC). Stable RhoA knockdown of TSCC cell lines SCC-4 and CAL27 were achieved using Lentiviral transfection. The effects of RhoA depletion on cell migration, invasion, and cell proliferation were determined. The possible underlying mechanism of RhoA depletion on TSCC cell line was also evaluated by determining the expression of Galectin-3 (Gal-3), β-catenin, and matrix metalloproteinase-9 (MMP-9) in vivo. Meanwhile, the underlying mechanism of TSCC growth was studied by analysis of cyclin D1/2, p21CIP1/WAF1, and p27Kip1 protein levels. Immunohistochemical assessments were performed to further prove the alteration of Gal-3 and β-catenin expression. We found that, in mice injected with human TSCC cells in the tongue, RhoA levels were higher in primary tumors and metastasized lymph nodes compared with those in the normal tissues. Silencing of RhoA significantly reduced the tumor growth, decreased the levels of Gal-3, β-catenin, MMP-9, and cyclin D1/2, and increased the levels of p21CIP1/WAF1 and p27Kip1. In vitro, RhoA knockdown also led to inhibition of cell migration, invasion, and proliferation. Our data suggest that RhoA plays a significant role in TSCC progression by regulating cell migration and invasion through Wnt/β-catenin signaling pathway and cell proliferation through cell cycle regulation, respectively. RhoA might be a novel therapeutic target of TSCC.
authors.forename: Guoxin
authors.initials: G
authors.lastname: Yan
authors.forename: Ronghai
authors.initials: R
authors.lastname: Zou
authors.forename: Zhenggang
authors.initials: Z
authors.lastname: Chen
authors.forename: Bing
authors.initials: B
authors.lastname: Fan
authors.forename: Zhaoyan
authors.initials: Z
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Yin
authors.forename: Dong
authors.initials: D
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Tong
authors.forename: Fang
authors.initials: F
authors.lastname: Yang
authors.forename: Weina
authors.initials: W
authors.lastname: Jiang
authors.forename: Wensheng
authors.initials: W
authors.lastname: Fu
authors.forename: Jiwei
authors.initials: J
authors.lastname: Zheng
authors.forename: Martin O
authors.initials: MO
authors.lastname: Bergo
authors.forename: Martin
authors.initials: M
authors.lastname: Dalin
authors.forename: Jiawei
authors.initials: J
authors.lastname: Zheng
authors.forename: Shulan
authors.initials: S
authors.lastname: Chen
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhou
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D037502:Galectin 3 / Q000378:metabolism; D020868:Gene Silencing; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009361:Neoplasm Invasiveness / Q000235:genetics*; D009362:Neoplasm Metastasis / Q000235:genetics*; D014062:Tongue Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000235:genetics*
chemical_list: D037502:Galectin 3; D051153:Wnt Proteins; D051176:beta Catenin; D020780:Matrix Metalloproteinase 9; D020742:rhoA GTP-Binding Protein