标题：Silencing RhoA inhibits migration and invasion through Wnt/beta-catenin pathway and growth through cell cycle regulation in human tongue cancer
作者：Yan, Guoxin; Zou, Ronghai; Chen, Zhenggang; Fan, Bing; Wang, Zhaoyan; Wang, Ying; Yin, Xiaonan; Zhang, Dong; Tong, Lei; Yang, Fang; 更多 作者机构：[Yan Guoxin] Department of Stomatology,Wuxi No.2 Peoples Hospital, Wuxi, Jiangsu 214002, China.;[Zou Ronghai] Department of Stomatology,Wuxi No.2 Peop 更多
通讯作者地址：[Zheng, JW]Shanghai Jiao Tong Univ, Peoples Hosp 9, Dept Oral & Maxillofacial Surg, Coll Stomatol,Sch Med, Shanghai 200011, Peoples R China.
关键词：RhoA; tumor invasion; metastasis; tumor growth; Wnt/beta-catenin; signaling pathway
摘要：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), beta-catenin, and matrix metalloproteinase-9 (MMP-9) in vivo. Meanwhile, the underlying mechanism of TSCC growth was studied by analysis of cyclin D1/2, p21(CIP1/WAF1), and p27(Kip1) protein levels. Immunohistochemical assessments were performed to further prove the alteration of Gal-3 and beta-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, beta-catenin, MMP-9, and cyclin D1/2, and increased the levels of p21(CIP1/WAF1) and p27(Kip1). 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/beta-catenin signaling pathway and cell proliferation through cell cycle regulation, respectively. RhoA might be a novel therapeutic target of TSCC.