CXXC finger protein 4 inhibits the CDK18‐ERK1/2 axis to suppress the immune escape of gastric cancer cells with involvement of ELK1/MIR100HG pathway
Authors: Junfeng Chu
Xiang Gu
Fangyong Hu
Ali Wang
Guangyu Tian
Pengfei Li
Ping Li
Dongfang Ge
Xiaojun Chen
Wenbo Song
Journal: Journal of Cellular and Molecular Medicine (2020)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: CXXC finger protein 4; ETS domain-containing protein-1; gastric cancer; immune escape; long non-coding RNA MIR100HG.
Affiliations: Department of Central Laboratory, Huaian Tumor Hospital & Huaian Hospital of Huaian City, Huaian, China., Department of General Surgery, Huaian Tumor Hospital & Huaian Hospital of Huaian City, Huaian, China., Department of Experimental Surgery-Cancer Metastasis, Medical Faculty Mannheim, Ruprecht Karls University, Mannheim, Germany., Department of Oncology, Jiangdu People's Hospital Affiliated to Medical College of Yangzhou University, Yangzhou, China.

Abstract:  Gastric cancer, is the fourth most common tumour type yet, ranks second in terms of the prevalence of cancer-related deaths worldwide. CXXC finger protein 4 (CXXC4) has been considered as a novel cancer suppressive factor, including gastric cancer. This study attempted to investigate the possible function of CXXC4 in gastric cancer and the underlying mechanism. The binding of the ETS domain-containing protein-1 (ELK1) to the long non-coding RNA MIR100HG promoter region was identified. Then, their expression patterns in gastric cancer tissues and cells (SGC7901) were detected. A CCK-8 assay was used to detect SGC7901 cell proliferation. Subsequently, SGC7901 cells were co-cultured with CD3+ T cells, followed by measurement of CD3+ T cell proliferation, magnitude of IFN-γ+ T cell population and IFN-γ secretion. A nude mouse model was subsequently developed for in vivo validation of the in vitro results. Low CXXC4 expression was found in SGC7901 cells. Nuclear entry of ELK1 can be inhibited by suppression of the extent of ELK1 phosphorylation. Furthermore, ELK1 is able to bind the MIR100HG promoter. Overexpression of CXXC4 resulted in weakened binding of ELK1 to the MIR100HG promoter, leading to a reduced proliferative potential of SGC7901 cells, and an increase in IFN-γ secretion from CD3+ T cells. Moreover, in vivo experiments revealed that CXXC4 inhibited immune escape of gastric cancer cells through the ERK1/2 axis. Inhibition of the CXXC4/ELK1/MIR100HG pathway suppressed the immune escape of gastric cancer cells, highlighting a possible therapeutic target for the treatment of gastric cancer. 

Retracted: No

PubPeer comments:
 Fig 4G.  The proliferation ability and the proportion of activated IFN-u03b3+ T cells of CD3+ detected by flow cytometry . ![file] Fig 5F.  The proliferation of CD3+ T cells and the proportion of IFN-u03b3+ T cells measured by flow cytometry, n = 3. ![file] Some overhangs noted. Were these hand-drawn? , 
  Acknowledgements We would like to thank our researchers for their hard work and reviewers for their valuable advice. I am puzzled. Are the authors thanking themselves? Or are they thanking some other people who **did the research** but do not warrant co-authorship or even acknowledgement by name? ,