Cholesterol-Mediated Remodelling of the Tumour-Immune Landscape: The Role of Non-Coding RNAs

Deborah Joyce¹, Wan Muhammad Farhan Syafiq Wan Mohd Nor², Ivy Chung², Amira Hajirah Abd Jamil¹, Nur Akmarina Mohd Said^1,*
1 Department of Pharmaceutical Life Sciences, Faculty of Pharmacy, Universiti Malaya, Kuala Lumpur, Malaysia
2 Department of Pharmacology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia
* Corresponding Author: Nur Akmarina Mohd Said. Email: email

BIOCELL https://doi.org/10.32604/biocell.2026.077378

Received 08 December 2025; Accepted 09 March 2026; Published online 23 March 2026

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Abstract

Non-coding RNAs (ncRNAs) and cholesterol metabolism have independently been recognized as critical regulators of cancer progression. NcRNAs modulate various aspects of cancer cell behaviour, including metabolic reprogramming, proliferation, migration, and intercellular communication. Concurrently, dysregulated cholesterol metabolism has emerged as a hallmark of cancer, influencing tumour growth, immune evasion, chemoresistance, and metastasis. While numerous studies have explored the role of ncRNAs like long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) in modulating cholesterol metabolism within either cancer cells or immune cells, the mechanism of their action largely depends on the involvement of microRNAs (miRNAs). However, the bidirectional metabolic crosstalk between cancer and immune cells involving miRNAs remains poorly understood. This review consolidates current knowledge on the participation of miRNAs in the dysregulation of cholesterol metabolism in both cancer and immune cells within the tumour microenvironment (TME). In particular, we focus on how intercellular communication involving miRNAs drives metabolic changes that contribute to immune cell reprogramming and the remodelling of the tumour-immune landscape. We further discuss the roles of cholesterol metabolites in facilitating such intercellular communication. By addressing this underexplored intersection, we aim to highlight potential miRNA targets and pathways that could inform future cancer immunotherapy strategies.