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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.

journal_name

Acta Biochim Biophys Sin (Shanghai)

journal_title

Acta biochimica et biophysica Sinica

authors

Yan G,Zou R,Chen Z,Fan B,Wang Z,Wang Y,Yin X,Zhang D,Tong L,Yang F,Jiang W,Fu W,Zheng J,Bergo MO,Dalin M,Zheng J,Chen S,Zhou J

doi

10.1093/abbs/gmu051

subject

Has Abstract

pub_date

2014-08-01 00:00:00

pages

682-90

issue

eissn

1672-9145

issn

1745-7270

pii

gmu051

journal_volume

pub_type

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Silencing RhoA inhibits migration and invasion through Wnt/β-catenin pathway and growth through cell cycle regulation in human tongue cancer.