1. Academic Validation
  2. CHAF1A interacts with TCF4 to promote gastric carcinogenesis via upregulation of c-MYC and CCND1 expression

CHAF1A interacts with TCF4 to promote gastric carcinogenesis via upregulation of c-MYC and CCND1 expression

  • EBioMedicine. 2018 Dec;38:69-78. doi: 10.1016/j.ebiom.2018.11.009.
Lixin Zheng 1 Xiuming Liang 2 Shuyan Li 3 Tongyu Li 3 Wenjing Shang 3 Lin Ma 3 Xiaxia Jia 3 Wei Shao 3 Pengpeng Sun 3 Chunyan Chen 4 Jihui Jia 5
Affiliations

Affiliations

  • 1 Department of Microbiology/Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, School of Basic Medical Science, Shandong University, Jinan, Shandong 250012, PR China; Key Laboratory of Infection and Immunity of Shandong Province, School of Basic Medical Science, Shandong University, Jinan, Shandong 250012, PR China.
  • 2 Department of Microbiology/Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, School of Basic Medical Science, Shandong University, Jinan, Shandong 250012, PR China; Shandong University-Karolinska Institutet Collaborative Laboratory for Cancer Research, Jinan, Shandong 250012, PR China.
  • 3 Department of Microbiology/Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, School of Basic Medical Science, Shandong University, Jinan, Shandong 250012, PR China.
  • 4 Cancer Center, Qilu Hospital, Shandong University, Jinan, Shandong 250012, PR China.
  • 5 Department of Microbiology/Key Laboratory for Experimental Teratology of the Chinese Ministry of Education, School of Basic Medical Science, Shandong University, Jinan, Shandong 250012, PR China; Key Laboratory of Infection and Immunity of Shandong Province, School of Basic Medical Science, Shandong University, Jinan, Shandong 250012, PR China; Shandong University-Karolinska Institutet Collaborative Laboratory for Cancer Research, Jinan, Shandong 250012, PR China. Electronic address: jiajihui@sdu.edu.cn.
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.

Keywords

CHAF1A; Carcinogenesis; Gastric cancer; Histone chaperone.

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