Zinc Finger Protein CTCF Regulates Extracellular Matrix (ECM)-Related Gene Expression Associated With the Wnt Signaling Pathway in Gastric Cancer

Chenbin Liu, Linyi Deng, Jinrong Lin, Jianjun Zhang, Shu Huang, Jinglin Zhao, Peipei Jin, Peiqing Xu, Peihua Ni, Dakang Xu, Le Ying, Yiqun Hu

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11 Citations (Scopus)

Abstract

Gastric cancer (GC), a leading cause of cancer-related death, is a heterogeneous disease. We aim to describe clinically relevant molecular classifications of GC that incorporate heterogeneity and provide useful clinical information. We combined different gene expression datasets and filtered a 7-gene signature related to the extracellular matrix (ECM), which also exhibited significant prognostic value in GC patients. Interestingly, putative CCCTC-binding factor (CTCF) regulatory elements were identified within the promoters of these ECM-related genes and were confirmed by chromatin immunoprecipitation sequencing (ChIP-Seq). CTCF binding sites also overlapped with histone activation markers, indicating direct regulation. In addition, CTCF was also correlated with the Wnt signaling pathway. A comparison of human GC cell lines with high or low expression of ECM-related genes revealed different levels of tumor aggressiveness, suggesting the cancer development-promoting functions of ECM-related genes. Furthermore, CTCF regulated COL1A1 and COLA31 expression in vitro. Silencing CTCF or COL1A1/COL1A3 markedly inhibited cell growth and migration in the metastatic GC cell line BGC823. Collectively, this ECM-related 7-gene signature provides a novel insight for survival prediction among GC patients. The zinc finger protein CTCF regulates ECM-related genes, thereby promoting GC cell growth and migration.

Original languageEnglish
Article number625633
Number of pages14
JournalFrontiers in Oncology
Volume10
DOIs
Publication statusPublished - 16 Feb 2021

Keywords

  • extracellular matrix (ECM)
  • gastric cancer
  • histone modification
  • Wnt signaling
  • zinc finger protein CTCF

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