Format

Send to

Choose Destination
Nat Commun. 2019 Jan 10;10(1):112. doi: 10.1038/s41467-018-07998-x.

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

Zhu GF1,2,3, Xu YW1,2,3, Li J1,2,3, Niu HL1,2,3, Ma WX1,2,3, Xu J4, Zhou PR2,5, Liu X1,2,3, Ye DL1,2,3, Liu XR1,2,3, Yan T2,5, Zhai WK1,2,3, Xu ZJ2,5, Liu C2,5, Wang L1,2, Wang H2,5, Luo JM2,5, Liu L6, Li XQ2, Guo S7, Jiang HP7, Shen P8, Lin HK9, Yu DH10, Ding YQ11,12,13, Zhang QL14,15,16.

Author information

1
Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, GuangDong, 510515, China.
2
Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, GuangDong, 510515, China.
3
Key Laboratory of Molecular Tumor Pathology of Guangdong Province, Guangzhou, GuangDong, 510515, China.
4
Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, 10029, USA.
5
Nanfang Hospital/First clinical Medical School, Southern Medical University, Guangzhou, GuangDong, 510515, China.
6
Hepatology Unit and Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, GuangDong, 510515, China.
7
Department of Obstetrics and Gynecology, The Third Affiliated Hospital, Southern Medical University, Guangzhou, GuangDong, 510630, China.
8
Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, GuangDong, 510515, China.
9
Cancer Biology Comprehensive Cancer Center, Wake Forest Baptist Medical Center, Winston-Salem, NC, 27157, USA.
10
Department of Molecular & Cellular Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX, 77030, USA.
11
Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, GuangDong, 510515, China. dyq@smu.edu.cn.
12
Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, GuangDong, 510515, China. dyq@smu.edu.cn.
13
Key Laboratory of Molecular Tumor Pathology of Guangdong Province, Guangzhou, GuangDong, 510515, China. dyq@smu.edu.cn.
14
Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, GuangDong, 510515, China. zqllc8@smu.edu.cn.
15
Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, GuangDong, 510515, China. zqllc8@smu.edu.cn.
16
Key Laboratory of Molecular Tumor Pathology of Guangdong Province, Guangzhou, GuangDong, 510515, China. zqllc8@smu.edu.cn.

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.

PMID:
30631060
PMCID:
PMC6328557
DOI:
10.1038/s41467-018-07998-x
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center