Mir20a/106a-WTX axis regulates RhoGDIa/CDC42 signaling and colon cancer progression

• Published in: Nature communications Vol. 10; no. 1; p. 112
• Main Authors: Zhu, Gui-Fang, Xu, Yang-Wei, Li, Jian, Niu, Hui-Lin, Ma, Wen-Xia, Xu, Jia, Zhou, Pei-Rong, Liu, Xia, Ye, Dan-Li, Liu, Xiao-Rong, Yan, Tao, Zhai, Wei-Ke, Xu, Zhi-Jun, Liu, Chun, Wang, Lei, Wang, Hao, Luo, Jia-Mao, Liu, Li, Li, Xuan-Qi, Guo, Suiqun, Jiang, Hui-Ping, Shen, Peng, Lin, Hui-Kuan, Yu, Di-Hua, Ding, Yan-Qing, Zhang, Qing-Ling
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 10.01.2019; Nature Publishing Group UK
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; Animals; Cancer; Cascades; cdc42 GTP-Binding Protein - genetics; cdc42 GTP-Binding Protein - metabolism; Cdc42 protein; Cell Line, Tumor; Cell proliferation; Colon; Colon cancer; Colonic Neoplasms - genetics; Colonic Neoplasms - metabolism; Colonic Neoplasms - pathology; Colorectal cancer; Colorectal carcinoma; Disease Progression; Female; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; HCT116 Cells; HT29 Cells; Humans; In vivo methods and tests; Liver; Male; Metastases; Metastasis; Mice, Inbred BALB C; Mice, Nude; MicroRNAs - genetics; Middle Aged; rho Guanine Nucleotide Dissociation Inhibitor alpha - genetics; rho Guanine Nucleotide Dissociation Inhibitor alpha - metabolism; Signal Transduction - genetics; Therapeutic applications; Transplantation, Heterologous; Tumor suppressor genes; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism; Tumors; X chromosomes
• ISSN: 2041-1723
• DOI: 10.1038/s41467-018-07998-x

Wilms tumor gene on the X chromosome (WTX) is a putative tumor suppressor gene in Wilms tumor, but its expression and functions in other tumors are unclear. Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in women and the second leading cause in men in the United States. We demonstrated that WTX frequently lost in CRC which was highly correlated with cell proliferation, tumor invasion and metastasis. Mechanistically, WTX loss disrupts the interaction between RhoGDIα and CDC42 by losing of the binding with RhoGDIα and triggers the activation of CDC42 and its downstream cascades, which promotes CRC development and liver metastasis. The aberrant upregulation of miR-20a/miR-106a were identified as the reason of WTX loss in CRC both in vivo and in vitro. These study defined the mechanism how miR-20a/miR-106a-mediated WTX loss regulates CRC progression and metastasis, and provided a potential therapeutic target for preventing CRC progression.