ARID1A downregulation promotes cell proliferation and migration of colon cancer via VIM activation and CDH1 suppression

J Cell Mol Med. 2022 Dec;26(24):5984-5997. doi: 10.1111/jcmm.17590. Epub 2022 Nov 24.


According to our prior findings, ARID1A expression is decreased in colon cancer, which has a poor prognosis. In this study, we investigated the ARID1A-VIM/CDH1 signalling axis's role in colon cancer proliferation and migration. The differentially expressed genes in cells that might be controlled by ARID1A were discovered by a database screening for ARID1A knockout. qPCR was used to analyse ARID1A and EMT markers expression levels in colon cancer. We utilized siRNA RID1A to explore the influence of ARID1A silencing on EMT in CRC cells. The function of ARID1A in the colon was investigated utilizing the wound healing, transwell and CCK-8 WST- assays. The molecular mechanism by which ARID1A regulates VIM and CDH1 was elucidated using chip-qPCR. Numerous genes involved in EMT were dysregulated in the absence of ARID1A. VIM expression increased in cells lacking ARID1A expression and vice versa. Many COAD samples with high ARID1A mRNA expression had low VIM mRNA expression, despite the relevance. CDH1 gene was positively correlated with ARID1A. Moreover, siRNA-ARID1A-transfected cells accelerated cell migration and invasion and increased cell proliferation rate in vitro. Chip-qPCR analysis showed that ARID1A binds to the promoters of both genes and changes their expression in colon cancer. ARID1A inactivation is associated with VIM activation and CDH1 suppression, which might serve as crucial molecules influencing COAD prognosis, accelerate tumour progression, and shorten patients' survival time, and promote metastases of COAD. Thus, depletion of ARID1A can be therapeutically exploited by targeting downstream effects to improve cancer treatment-related outcomes.

Keywords: ARID1A knockdown; CDH1; VIM; colon cancer; invasion; migration.

MeSH terms

  • Antigens, CD / genetics
  • Cadherins / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Colonic Neoplasms* / genetics
  • DNA-Binding Proteins / genetics
  • Down-Regulation / genetics
  • Epithelial-Mesenchymal Transition* / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • RNA, Messenger
  • RNA, Small Interfering / genetics
  • Transcription Factors / genetics


  • RNA, Small Interfering
  • RNA, Messenger
  • ARID1A protein, human
  • DNA-Binding Proteins
  • Transcription Factors
  • CDH1 protein, human
  • Antigens, CD
  • Cadherins