ARID3A Dysregulation Drives Colon Cancer Progression and Enhances Responsiveness to Aspirin

TL;DR

ARID3A promotes colon cancer growth and makes cancer cells more responsive to aspirin treatment.

Contribution

This study identifies ARID3A as a key driver of colon cancer and a potential biomarker for aspirin therapy.

Findings

ARID3A is upregulated in colon cancer and promotes cell proliferation, migration, and invasion.

ARID3A enhances PGE2 synthesis and macrophage infiltration in colon cancer.

Aspirin reduces PGE2 levels and inhibits the malignant behavior of ARID3A-overexpressing cells.

Abstract

The AT‐Rich Interaction Domain (ARID) family plays critical roles in malignancies. Although numerous members have been shown to influence cancer processes, there is a lack of a general understanding of the ARID family in colon cancer. To address this gap, we used bioinformatic technologies to investigate the role of the ARID family as a whole and to identify the crucial member. Subsequently, cell growth assays, transwell assays, and animal models were employed to validate the key member's effect on colon cancer growth and metastasis. Furthermore, bioinformatics and immunohistochemistry were utilised to explore the potential mechanisms and evaluate the efficacy of a targeted intervention strategy. Our results showed that the ARID family was upregulated in colon cancer, with ARID3A being the main component that promoted colon cancer development. Specifically, ARID3A enhanced colon cancer cell proliferation, migration, and invasion both in vivo and in vitro. Mechanistically, this promotional effect could be associated with ARID3A promoting PGE2 synthesis and triggering macrophage infiltration. Notably, aspirin treatment reduced the PGE2 level, which significantly inhibited the malignant behaviour of ARID3A‐overexpressing cells. In conclusion, ARID3A was a key member of the ARID family in the development of colon cancer. ARID3A was an underlying biomarker for aspirin administration.

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