MicroRNA clusters as regulators in progressive fatty liver disease Spectrum: from mechanistic insights to therapeutic opportunities.

[BACKGROUND AND AIM] Metabolic dysfunction-associated steatotic liver disease (MASLD)-Hepatocellular carcinoma (HCC) is a progressive metabolic condition that affects the function of liver, marked by various molecular changes. While it is appreciated that markers like microRNAs exist as polycistronic clusters (miRCs), their involvement in MASLD spectrum is not completely understood. This review provides a comprehensive understanding of the association of miRNA clusters in MASLD-HCC and discusses the potential therapeutic window for targeting miRCs in the clinical management of this progressive liver disease.

[METHODOLOGY] Relevant literature was searched in PUBMED and Google Scholar databases using the search string miRNA cluster, along with MASLD, MASH, HCC, diagnosis, and prognosis.

[RESULTS] Several critical miRCs were identified to be associated with the MASLD-HCC spectrum. In MASLD and MASH, miR-379/544, miR-23-24-27 were identified to be reported. In HCC, miR-17-92, miR-106b/25, mir-23-24-27, miR-216a/217, miR-545/374a, miR-183/96/182, miR-221/222 clusters were identified as oncogenic clusters, and miR-15a-16-1, miR-497/195, miR-143/145, miR-244/199a, miR-379/656, let-7c/miR-99a, and miR-302a/b/c clusters were identified as tumor suppressor clusters. Of these, miR-23-24-27 was identified to be clinically relevant in MASLD. miR-17-92 and miR-379/656 clusters were reported to be clinically relevant in HCC.

[CONCLUSION] miRCs are critical drivers of MASLD-HCC pathogenesis and progression, and targeting them can be useful to develop specific diagnostic and prognostic panels for this progressive liver condition.