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

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

doi:10.1038/s41467-018-07998-x

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

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

Authors

Gui-Fang Zhu^{1

2

3}, Yang-Wei Xu^{1

2

3}, Jian Li^{1

2

3}, Hui-Lin Niu^{1

2

3}, Wen-Xia Ma^{1

2

3}, Jia Xu⁴, Pei-Rong Zhou^{2

5}, Xia Liu^{1

2

3}, Dan-Li Ye^{1

2

3}, Xiao-Rong Liu^{1

2

3}, Tao Yan^{2

5}, Wei-Ke Zhai^{1

2

3}, Zhi-Jun Xu^{2

5}, Chun Liu^{2

5}, Lei Wang^{1

2}, Hao Wang^{2

5}, Jia-Mao Luo^{2

5}, Li Liu⁶, Xuan-Qi Li², Suiqun Guo⁷, Hui-Ping Jiang⁷, Peng Shen⁸, Hui-Kuan Lin⁹, Di-Hua Yu¹⁰, Yan-Qing Ding^{11

12

13}, Qing-Ling Zhang^{14

15

16}

Affiliations

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. [email protected].
¹² Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, GuangDong, 510515, China. [email protected].
¹³ Key Laboratory of Molecular Tumor Pathology of Guangdong Province, Guangzhou, GuangDong, 510515, China. [email protected].
¹⁴ Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, GuangDong, 510515, China. [email protected].
¹⁵ Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, GuangDong, 510515, China. [email protected].
¹⁶ Key Laboratory of Molecular Tumor Pathology of Guangdong Province, Guangzhou, GuangDong, 510515, China. [email protected].

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.

Publication types

Research Support, Non-U.S. Gov't
Retracted Publication

MeSH terms

Adaptor Proteins, Signal Transducing / genetics*
Adaptor Proteins, Signal Transducing / metabolism
Animals
Cell Line, Tumor
Colonic Neoplasms / genetics*
Colonic Neoplasms / metabolism
Colonic Neoplasms / pathology
Disease Progression
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
HCT116 Cells
HT29 Cells
Humans
Male
Mice, Inbred BALB C
Mice, Nude
MicroRNAs / genetics*
Middle Aged
Signal Transduction / genetics
Transplantation, Heterologous
Tumor Suppressor Proteins / genetics*
Tumor Suppressor Proteins / metabolism
cdc42 GTP-Binding Protein / genetics*
cdc42 GTP-Binding Protein / metabolism
rho Guanine Nucleotide Dissociation Inhibitor alpha / genetics*
rho Guanine Nucleotide Dissociation Inhibitor alpha / metabolism

Substances

AMER1 protein, human
Adaptor Proteins, Signal Transducing
MIRN106 microRNA, human
MIRN20a microRNA, human
MicroRNAs
Tumor Suppressor Proteins
rho Guanine Nucleotide Dissociation Inhibitor alpha
CDC42 protein, human
cdc42 GTP-Binding Protein

Grants and funding

T32 CA078207/CA/NCI NIH HHS/United States