Regulation of TRIM24 by miR-511 modulates cell proliferation in gastric cancerReport as inadecuate




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Journal of Experimental and Clinical Cancer Research

, 36:17

First Online: 23 January 2017Received: 29 September 2016Accepted: 05 January 2017DOI: 10.1186-s13046-017-0489-1

Cite this article as: Fang, Z., Zhang, L., Liao, Q. et al. J Exp Clin Cancer Res 2017 36: 17. doi:10.1186-s13046-017-0489-1

Abstract

BackgroundIncreasing evidence highlights the important roles of tripartite motif containing 24 TRIM24 in tumor initiation and malignant progression in many tumors, including gastric cancer GC. Although TRIM24 expression is remarkably upregulated during GC carcinogenesis, the molecular mechanisms underlying TRIM24 dysregulation remain unexplored.

MethodsIn this study, miRNA target prediction tools were applied to explore miRNAs that potentially target TRIM24. Western blot and quantitative reverse-transcriptase PCR qRT-PCR were performed to detected TRIM24 and miR-511 expression in GC tissues and cell lines. Dual-luciferase reporter assay was utilized to validate if TRIM24 is a direct target gene of miR-511. CCK-8 assay, cell colony formation assay, EdU incorporation assay and cell cycle analysis were performed to determine whether miR-511-mediated regulation of TRIM24 could affect GC progression.

ResultsIn our study, miR-511 was found to be downregulated in GC and an inverse correlation was observed between TRIM24 and miR-511 expression in primary GC tissues and cell lines. Dual-luciferase reporter assay further verified TRIM24 is a direct target of miR-511. Functional assays showed miR-511 overexpression inhibited cell growth, colony formation ability and cell cycle progression. Conversely, inhibition of endogenous miR-511 promoted these phenotypes in GC cells. Moreover, reintroduction of TRIM24 rescued miR-511-induced inhibitory effects on GC cells. Furthermore, miR-511 elicits tumor-suppressive effects through inactivating PI3K-AKT and Wnt-β-catenin pathways by suppressing TRIM24.

ConclusionsOur results provide the new evidence supporting the tumor-suppressive role of miR-511 in GC by suppressing TRIM24, suggesting that this novel miR-511-TRIM24 axis is critical in the control of gastric cancer tumorigenesis.

KeywordsmiR-511 TRIM24 Cell proliferation Gastric cancer AbbreviationsGCGastric cancer

miRNAmicroRNAs

qRT-PCRQuantitative reverse-transcriptase polymerase chain reaction

TRIM24Tripartite motif containing 24

Electronic supplementary materialThe online version of this article doi:10.1186-s13046-017-0489-1 contains supplementary material, which is available to authorized users.

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Author: Ziling Fang - Ling Zhang - Quan Liao - Yi Wang - Feng Yu - Miao Feng - Xiaojun Xiang - Jianping Xiong

Source: https://link.springer.com/







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