TRIM27 acts as an oncogene and regulates cell proliferation and metastasis in non-small cell lung cancer through SIX3-β-catenin signaling

Shiyuan Liu; Ying Tian; Ying Zheng; Yao Cheng; Danjie Zhang; Jiantao Jiang; Shaomin Li

doi:10.18632/aging.104163

TRIM27 acts as an oncogene and regulates cell proliferation and metastasis in non-small cell lung cancer through SIX3-β-catenin signaling

Aging (Albany NY). 2020 Dec 2;12(24):25564-25580. doi: 10.18632/aging.104163. Epub 2020 Dec 2.

Authors

Shiyuan Liu¹, Ying Tian², Ying Zheng³, Yao Cheng¹, Danjie Zhang¹, Jiantao Jiang¹, Shaomin Li¹

Affiliations

¹ Department of Thoracic Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, China.
² Xi'an Jiaotong University Press, Xi'an 710049, China.
³ Xi'an Jiaotong University School of Medicine, Xi'an 710061, China.

Abstract

The Wnt/β-catenin pathway plays vital roles in diverse biological processes, including cell differentiation, proliferation, migration, and insulin sensitivity. A recent study reported that the DNA-binding transcriptional factor SIX3 is essential during embryonic development in vertebrates and capable of downregulating target genes of the Wnt/β-catenin pathway in lung cancer, indicating negative regulation of Wnt/β-catenin activation. However, regulation of the SIX3-Wnt/β-catenin pathway axis remains unknown. We measured the expression of TRIM27 and SIX3 as well as investigated whether there was a correlation between them in lung cancer tissue samples. Herein, we found that the E3 ubiquitin ligase, TRIM27, ubiquitinates, and degrades SIX3. TRIM27 induces non-small cell lung cancer (NSCLC) cell proliferation and metastasis, and the expression of β-catenin, S100P, TGFB3, and MMP-9 were significantly inhibited by SIX3. Furthermore, XAV939 is a selective β-catenin-mediated transcription inhibitor that inhibited TRIM27- and SIX3-mediated NSCLC cell proliferation, migration, and invasion. Clinically, lung tissue samples of cancer patients showed increased TRIM27 expression and decreased SIX3 expression. Taken together, these data demonstrate that TRIM27 acts as an oncogene regulating cell proliferation and metastasis in NSCLC through SIX3-β-catenin signaling.

Keywords: SIX3; TRIM27; lung cancer; ubiquitination; β-catenin.

Publication types

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

MeSH terms

A549 Cells
Calcium-Binding Proteins / drug effects
Calcium-Binding Proteins / metabolism
Carcinoma, Non-Small-Cell Lung / genetics*
Carcinoma, Non-Small-Cell Lung / metabolism
Carcinoma, Non-Small-Cell Lung / pathology
Cell Movement / drug effects
Cell Movement / genetics
Cell Proliferation / drug effects
Cell Proliferation / genetics*
DNA-Binding Proteins / genetics*
DNA-Binding Proteins / metabolism
Eye Proteins / genetics*
Eye Proteins / metabolism
Female
Heterocyclic Compounds, 3-Ring / pharmacology
Homeobox Protein SIX3
Homeodomain Proteins / genetics*
Homeodomain Proteins / metabolism
Humans
Lung Neoplasms / genetics*
Lung Neoplasms / metabolism
Lung Neoplasms / pathology
Male
Matrix Metalloproteinase 9 / drug effects
Matrix Metalloproteinase 9 / metabolism
Middle Aged
Neoplasm Metastasis
Neoplasm Proteins / drug effects
Neoplasm Proteins / metabolism
Nerve Tissue Proteins / genetics*
Nerve Tissue Proteins / metabolism
Nuclear Proteins / genetics*
Nuclear Proteins / metabolism
Oncogenes
Signal Transduction
Transforming Growth Factor beta3 / drug effects
Transforming Growth Factor beta3 / metabolism
Ubiquitination / drug effects
Ubiquitination / genetics
beta Catenin / drug effects
beta Catenin / metabolism

Substances

Calcium-Binding Proteins
DNA-Binding Proteins
Eye Proteins
Heterocyclic Compounds, 3-Ring
Homeodomain Proteins
Neoplasm Proteins
Nerve Tissue Proteins
Nuclear Proteins
S100P protein, human
TGFB3 protein, human
TRIM27 protein, human
Transforming Growth Factor beta3
XAV939
beta Catenin
MMP9 protein, human
Matrix Metalloproteinase 9