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

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.