<em>ARID1A</em> overexpression inhibits colorectal cancer cell migration through the regulation of epithelial‑mesenchymal transition

Wanna‑Udom,Sasithorn; Aluksanasuwan,Siripat; Somsuan,Keerakarn; Mongkolwat,Wariya; Sakulsak,Natthiya

doi:10.3892/mmr.2024.13325

ARID1A overexpression inhibits colorectal cancer cell migration through the regulation of epithelial‑mesenchymal transition

Authors:
- Sasithorn Wanna‑Udom
- Siripat Aluksanasuwan
- Keerakarn Somsuan
- Wariya Mongkolwat
- Natthiya Sakulsak
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Affiliations: Department of Anatomy, Faculty of Medical Science, Naresuan University, Phitsanulok 65000, Thailand, School of Medicine, Mae Fah Luang University, Chiang Rai 57100, Thailand
Published online on: September 6, 2024 https://doi.org/10.3892/mmr.2024.13325
Article Number: 201
Copyright: © Wanna‑Udom et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The advancement of tumor cell metastasis is significantly influenced by epithelial‑to‑mesenchymal transition (EMT), and metastasis is a prominent contributor to the mortality of patients diagnosed with colorectal cancer (CRC). AT‑rich interactive domain‑containing protein 1A (ARID1A), which acts as a tumor suppressor, frequently exhibits a loss‑of‑function mutation in metastatic CRC tissues. However, the underlying molecular mechanisms of ARID1A relating to EMT remain poorly understood. The present study aimed to clarify the association between ARID1A and EMT regulation in human CRC cells. The investigation into the loss of ARID1A expression in tissues from patients with CRC was performed using immunohistochemistry. Furthermore, ARID1A‑overexpressing SW48 cells were established using lentiviruses carrying human full‑length ARID1A. The results revealed that overexpression of ARID1A induced cellular morphological changes by promoting the tight junction molecule zonula occludens 1 (ZO‑1) and the adherens junction molecule E‑cadherin, whereas it decreased the intermediate filament protein vimentin. The results of reverse transcription‑quantitative PCR also confirmed that ARID1A overexpression upregulated the mRNA expression levels of TJP1/ZO‑1 and CDH1/E‑cadherin, and downregulated VIM/vimentin and zinc finger E‑box binding homeobox 1 expression, which are considered epithelial and mesenchymal markers, respectively. In addition, the overexpression of ARID1A in CRC cells resulted in a suppression of cell motility and migratory capabilities. The present study also demonstrated that the tumor suppressor ARID1A was commonly absent in CRC tissues. Notably, ARID1A overexpression could reverse the EMT‑like phenotype and inhibit cell migration through alterations in EMT‑related markers, leading to the inhibition of malignant progression. In conclusion, ARID1A may serve as a biomarker and therapeutic target in the clinical management of metastatic CRC.

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