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CHFR promotes the migration of human gastric cancer cells by inducing epithelial-to-mesenchymal transition in a HDAC1-dependent manner

Authors Yang S, He F, Dai M, Pan J, Wang J, Ye B

Received 15 October 2018

Accepted for publication 4 January 2019

Published 7 February 2019 Volume 2019:12 Pages 1075—1084


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4

Editor who approved publication: Dr William Cho

Shangwen Yang,1 Feiyun He,2 Mugen Dai,1 Jundi Pan,1 Jianbo Wang,1 Bin Ye1

1Department of Gastroenterology, The Fifth Affiliated Hospital of Wenzhou Medical University and Lishui Municipal Central Hospital, Lishui 323000, Zhejiang Province, China; 2Department of Gastroenterology, Lishui Chinese Medicine Hospital, Lishui 323000, Zhejiang Province, China

Background: Previous studies have illustrated that checkpoint with forkhead-associated and ring finger domains (CHFR) was frequently silenced in several cancer types due to promoter hypermethylation and functions as a tumor suppressor gene. However, the data from the public dataset reveal that CHFR is highly expressed in human gastric cancer specimens, and the biological function of CHFR in gastric cancer is still not well understood.
Materials and methods: The clinical association between CHFR expression and the overall survival of gastric cancer patients as well as cancer metastasis was analyzed according to public datasets. The CHFR expression in clinical specimens and human gastric cancer cell lines was detected by immunohistochemistry and Western blotting, respectively. Gain (overexpression) and loss (silencing) of function experiments were used to elucidate the role of CHFR in gastric cancer. The migration ability of gastric cancer cells was determined by wound healing and transwell assays. Cell cycle distribution was analyzed using fluorescence-activated cell sorting experiment. The expression of the proteins in cancer cells was measured using Western blot analysis.
Results: According to the analysis from Kaplan–Meier plotter dataset, CHFR expression was negatively associated with overall survival of gastric cancer patients. Our data revealed that exogenous expression of CHFR not only arrested cell cycle but also led to dramatically enhanced cell migration, while silencing of CHFR significantly inhibited cell migration in gastric cancer cells. This result is consistent with the data from the Human Cancer Metastasis Dataset, in which CHFR level is found to significantly increase in metastatic gastric cancer. The overexpression of CHFR promoted epithelial–mesenchymal transition (EMT) in both SGC-7901 and AGS cells, while HDAC1 was inhibited. Interestingly, suberoylanilide hydroxamic acid, a HDAC1 antagonist, could effectively increase cell migration in both cell lines via enhancement of EMT.
Conclusion: Our data indicated that CHFR exerted positive effects on cell migration of human gastric cancer by promoting EMT via downregulating HDAC1.

Keywords: human gastric cancer, migration, CHFR, EMT, HDAC1

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