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

Abstract

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.

Proteomic insights into the regulatory function of ARID1A in colon cancer cells

“…Previous studies have reported that ARID1A knockdown promotes carcinogenic behaviors ( 16 – 18 ), whilst its overexpression reverses such effects in CRC cells ( 19 ). These findings underscored the tumor suppressive role of ARID1A in CRC cells.…”

“…ARID1A is an essential component of the SWI/SNF chromatin remodeling complex, which serves a crucial role in modulating the structure and accessibility of DNA ( 18 ). The diverse functions of ARID1A have been extensively documented in previous studies.…”

“…ARID1A knockdown enhances the proliferation, migration, invasion and chemoresistance of CRC cells ( 16 , 17 ). Furthermore, ARID1A has been reported to promote the epithelial-mesenchymal transition (EMT) process by regulating the expression of vimentin and E-cadherin ( 18 , 19 ). However, the precise molecular mechanisms through which ARID1A regulates CRC carcinogenesis and progression are not yet fully understood.…”

SMP30 Interacts with ROCK1 to Inhibit HCC Invasiveness by Effecting the Epithelial-Mesenchymal Transition

“…MMP9 is involved in extracellular matrix degradation and EMT regulation, as well as tumor cell migration and invasion [30,31]. VIM is an intermediate filament cytoskeletal protein, and EMT is associated with increased VIM expression and decreased E-cadherin expression [32,33]. When recombinant SMP30 was overexpressed in SK-Hep-1 cells, increased expression of CDH1 and decreased expression of CDH2, MMP9, FN1, and VIM were observed.…”