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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-12

AUTHORS

Gui-fang Zhu, Yang-wei Xu, Jian Li, Hui-lin Niu, Wen-xia Ma, Jia Xu, Pei-rong Zhou, Xia Liu, Dan-li Ye, Xiao-rong Liu, Tao Yan, Wei-ke Zhai, Zhi-jun Xu, Chun Liu, Lei Wang, Hao Wang, Jia-mao Luo, Li Liu, Xuan-qi Li, Suiqun Guo, Hui-ping Jiang, Peng Shen, Hui-kuan Lin, Di-hua Yu, Yan-qing Ding, Qing-ling Zhang

ABSTRACT

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. More... »

PAGES

112

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41467-018-07998-x

DOI

http://dx.doi.org/10.1038/s41467-018-07998-x

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1111164769

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30631060


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83 schema:description 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.
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