TRIM16 overexpression inhibits the metastasis of colorectal cancer through mediating Snail degradation

Longhui Ruan; Weifeng Liu; Yanhui Yang; Zhijie Chu; Cheng Yang; Tianbao Yang; Junjun Sun

doi:10.1016/j.yexcr.2021.112735

TRIM16 overexpression inhibits the metastasis of colorectal cancer through mediating Snail degradation

Exp Cell Res. 2021 Sep 1;406(1):112735. doi: 10.1016/j.yexcr.2021.112735. Epub 2021 Jul 13.

Authors

Longhui Ruan¹, Weifeng Liu¹, Yanhui Yang¹, Zhijie Chu¹, Cheng Yang¹, Tianbao Yang¹, Junjun Sun²

Affiliations

¹ The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, China.
² The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, China. Electronic address: lyhnkjdx@163.com.

PMID: 34265287
DOI: 10.1016/j.yexcr.2021.112735

Abstract

Tripartite motif containing 16 (TRIM16) is a member of the tripartite motif protein family and functions as a potential tumor suppressor in several cancers. However, the specific function and clinical significance of TRIM16 in colorectal cancer (CRC) remains unclear. In this study, we observed that low TRIM16 expression was detected frequently in primary colorectal cancer (CRC) tissues and was closely associated with a better prognosis. Functional studies demonstrate that TRIM16 overexpression notably inhibits the metastasis abilities of CRC in vivo and in vitro. Mechanistically, our results demonstrated that TRIM16 directly bound and ubiquitinated Snail family transcriptional repressor 1 (Snail), an important transcriptional factor of the epithelial-mesenchymal transition (EMT) process suppressing the EMT in CRC. Additionally, our data revealed that the inhibition effect of TRIM16 on cancer metastasis was dependent on Snail degradation. Collectively, our study is the first to report that TRIM16 plays a crucial anti-tumor role in CRC tumorigenesis. We also provided novel evidence that TRIM16 might act as a prognostic and therapeutic target to assess and inhibit CRC progression.

Keywords: Cell migration; Colorectal cancer; EMT; TRIM16; Ubiquitination.

Publication types

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

MeSH terms

Animals
Carcinogenesis / genetics
Carcinogenesis / metabolism
Carcinogenesis / pathology
Carcinoma / genetics*
Carcinoma / metabolism
Carcinoma / mortality
Carcinoma / secondary
Cell Line, Tumor
Cell Movement
Cell Proliferation
Colorectal Neoplasms / genetics*
Colorectal Neoplasms / metabolism
Colorectal Neoplasms / mortality
Colorectal Neoplasms / pathology
Epithelial-Mesenchymal Transition / genetics
Gene Expression Regulation, Neoplastic
HCT116 Cells
Humans
Liver Neoplasms / genetics*
Liver Neoplasms / metabolism
Liver Neoplasms / mortality
Liver Neoplasms / secondary
Male
Matrix Metalloproteinase 9 / genetics
Matrix Metalloproteinase 9 / metabolism
Mice
Mice, Inbred BALB C
Mice, Nude
Prognosis
Proteolysis
RNA, Small Interfering / genetics
RNA, Small Interfering / metabolism
Snail Family Transcription Factors / genetics*
Snail Family Transcription Factors / metabolism
Survival Analysis
Tripartite Motif Proteins / antagonists & inhibitors
Tripartite Motif Proteins / genetics*
Tripartite Motif Proteins / metabolism
Tumor Burden
Ubiquitin-Protein Ligases / antagonists & inhibitors
Ubiquitin-Protein Ligases / genetics*
Ubiquitin-Protein Ligases / metabolism
Xenograft Model Antitumor Assays
Zinc Finger E-box-Binding Homeobox 1 / genetics
Zinc Finger E-box-Binding Homeobox 1 / metabolism

Substances

RNA, Small Interfering
SNAI1 protein, human
Snail Family Transcription Factors
Tripartite Motif Proteins
ZEB1 protein, human
Zinc Finger E-box-Binding Homeobox 1
TRIM16 protein, human
Ubiquitin-Protein Ligases
MMP9 protein, human
Matrix Metalloproteinase 9