MTA2-mediated inhibition of PTEN leads to pancreatic ductal adenocarcinoma carcinogenicity

Cell Death & Disease
Wenzhe SiTianpei Hong

Abstract

Metastasis-associated protein 2 (MTA2) is a core subunit of the nucleosome remodeling and deacetylating (NuRD) complex and functions by mediating chromatin remodeling and gene silencing. However, its biological actions and clinical significance in pancreatic ductal adenocarcinoma (PDAC) remain elusive. The aim of this study was to explore the function and regulation mechanism of MTA2 in PDAC. As shown in GEO, ICGC, and TCGA databases, a higher expression of MTA2 was noticed in the PDAC tissues than in the normal pancreatic tissues. Moreover, a higher expression level of MTA2 was associated with a shorter overall survival time in these public PDAC databases. We further investigated the underlying mechanisms of these observations by using a chromatin immunoprecipitation (ChIP)-based deep sequencing, luciferase reporter, and quantitative ChIP assays. We identified the repressive binding of MTA2 to the promoter of phosphatase and tensin homolog (PTEN). We also found that Snail recruited MTA2 and HDAC1 to suppress PTEN expression. Ectopic expression and knockdown of MTA2 were performed to evaluate the effects of this gene on PDAC cell proliferation, migration, and invasion. Using CCK-8, colony formation and transwell assays, and a x...Continue Reading

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Datasets Mentioned

BETA
MTA2

Methods Mentioned

BETA
pharmacotherapy
acetylation
ChIP
ChIP-seq
transfection
xenograft
PCR
immunoprecipitation
transfect

Software Mentioned

Illumina
SPSS
MACS ( Model - based Analysis for ChIP - Seq )
HiSeq2000

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