CHAF1A Interacts with TCF4 to Promote Gastric Carcinogenesis Via Upregulation of C-MYC and CCND1 Expression

Overview

Journal EBioMedicine

Specialty Biomedical Engineering

Date 2018 Nov 20

PMID 30449701

Citations 22

Authors

Lixin Zheng

Xiuming Liang

Shuyan Li

Tongyu Li

Wenjing Shang

Lin Ma

Xiaxia Jia

Wei Shao

Pengpeng Sun

Chunyan Chen

Jihui Jia

Affiliations

Soon will be listed here.

Abstract

Background: Histones chaperones have been found to play critical roles in tumor development and progression. However, the role of histone chaperone CHAF1A in gastric carcinogenesis and its underlying mechanisms remain elusive.

Methods: CHAF1A expression in gastric cancer (GC) was analyzed in GEO datasets and clinical specimens. CHAF1A knockdown and overexpression were used to explore its functions in gastric cancer cells. The regulation and potential molecular mechanism of CHAF1A expression in gastric cancer cells were studied by using cell and molecular biological methods.

Findings: CHAF1A was upregulated in GC tissues and its high expression predicted poor prognosis in GC patients. Overexpression of CHAF1A promoted gastric cancer cell proliferation both in vitro and in vivo, whereas CHAF1A suppression exhibited the opposite effects. Mechanistically, CHAF1A acted as a co-activator in the Wnt pathway. CHAF1A directly interacted with TCF4 to enhance the expression of c-MYC and CCND1 through binding to their promoter regions. In addition, the overexpression of CHAF1A was modulated by specificity protein 1 (Sp1) in GC. Sp1 transcriptionally enhanced the expression of CHAF1A in GC. Furthermore, CHAF1A expression induced by Helicobacter pylori was Sp1 dependent.

Interpretation: CHAF1A is a potential oncogene in GC, and may serve as a novel therapeutic target for GC treatment.

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