MAGI1 mediates tumor metastasis through c-Myb/miR-520h/MAGI1 signaling pathway in renal cell carcinoma

Wei Wang; Yanhua Yang; Xinyi Chen; Shihong Shao; Shasha Hu; Tingguo Zhang

doi:10.1007/s10495-019-01562-8

MAGI1 mediates tumor metastasis through c-Myb/miR-520h/MAGI1 signaling pathway in renal cell carcinoma

Apoptosis. 2019 Dec;24(11-12):837-848. doi: 10.1007/s10495-019-01562-8.

Authors

Wei Wang^{1

2}, Yanhua Yang³, Xinyi Chen^{4

5}, Shihong Shao², Shasha Hu², Tingguo Zhang^{6

7}

Affiliations

¹ Department of Pathology, Qilu Hospital, Shandong University, Jinan, Shandong, China.
² Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
³ Department of Pathology, Qingdao Municipal Hospital, Qingdao, Shandong, China.
⁴ Department of Pathology, Qingdao Central Hospital, Qingdao, Shandong, China.
⁵ Department of Pathology, The Second Affiliated Hospital of Qingdao University Medical College, Qingdao, Shandong, China.
⁶ Department of Pathology, Qilu Hospital, Shandong University, Jinan, Shandong, China. [email protected].
⁷ Department of Pathology, School of Basic Medical Sciences, Shandong University, NO. 44, Wenhuaxi Road, Jinan, Shandong, China. [email protected].

PMID: 31352641
DOI: 10.1007/s10495-019-01562-8

Abstract

Renal cell carcinoma (RCC) is the third most common urological cancer with highly metastatic potential. MAGI1 plays an important role in stabilization of the adherens junctions and has been confirmed to suppress invasiveness and metastasis in multiple cancers in clinic. However, its expression and anti-metastatic ability in RCC are still unclear. In this study, we demonstrated that MAGI1 was markedly decreased in the RCC and indicated poor survival. Furthermore, we found that MAGI1 suppressed the invasion and migration of human RCC cells. Mechanistic investigations revealed that MAGI1 stabilized the PTEN/MAGI1/β-catenin complex to inhibit β-catenin signaling pathway. Moreover, MAGI1 was targeted by miR-520h which was transcriptionally activated by c-Myb. Collectively, our findings suggested that MAGI1mediated tumor metastasis through c-Myb/miR-520h/MAGI1 signaling pathway in RCC.

Keywords: MAGI1; Metastasis; Renal cell carcinoma; c-Myb; miR-520h.

Publication types

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

MeSH terms

Adaptor Proteins, Signal Transducing / genetics
Adaptor Proteins, Signal Transducing / metabolism*
Carcinoma, Renal Cell / genetics
Carcinoma, Renal Cell / metabolism*
Carcinoma, Renal Cell / mortality
Carcinoma, Renal Cell / secondary
Cell Adhesion Molecules / genetics
Cell Adhesion Molecules / metabolism*
Cell Line, Tumor
Cell Movement / genetics
Female
Gene Expression Regulation, Neoplastic / genetics
Guanylate Kinases / genetics
Guanylate Kinases / metabolism*
Humans
Kidney Neoplasms / genetics
Kidney Neoplasms / metabolism*
Kidney Neoplasms / mortality
Kidney Neoplasms / pathology
Male
MicroRNAs / genetics
MicroRNAs / metabolism*
Middle Aged
Neoplasm Invasiveness / genetics
PTEN Phosphohydrolase / genetics
PTEN Phosphohydrolase / metabolism
Promoter Regions, Genetic
Proto-Oncogene Proteins c-myb / genetics
Proto-Oncogene Proteins c-myb / metabolism*
Signal Transduction / genetics
beta Catenin / genetics
beta Catenin / metabolism

Substances

Adaptor Proteins, Signal Transducing
Cell Adhesion Molecules
MIRN520 microRNA, human
MYB protein, human
MicroRNAs
Proto-Oncogene Proteins c-myb
beta Catenin
Guanylate Kinases
MAGI1 protein, human
PTEN Phosphohydrolase
PTEN protein, human

Grants and funding

21300005131323/National Natural Science Foundation of China/International