The role of non-coding RNA in metabolic dysfunction-associated steatosis liver and cardiovascular disease

Abstract

Non-coding RNAs (ncRNAs), including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), play critical roles in gene regulation without encoding proteins. miRNAs, typically 18–25 nucleotides long, bind to untranslated regions of target mRNAs, leading to degradation or translational repression.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a progressive condition beginning with steatosis and potentially advancing to inflammation (MASH), fibrosis, cirrhosis, or hepatocellular carcinoma (HCC). Its progression is influenced by lipotoxicity, ER stress, insulin resistance, and epigenetic changes. miR-34a is a key regulator in liver diseases, affecting lipid metabolism, apoptosis, and inflammation, and is linked to MASLD and fibrosis. However, its role in insulin resistance-associated liver fibrosis remains unclear.

Hepatocyte Nuclear Factor 4 alpha (HNF4α) is a transcription factor essential for lipid and glucose metabolism. It interacts with PPARα and AMPK to modulate insulin sensitivity, but its role in MASLD-related fibrosis is underexplored.


Moreover, metabolic syndrome also affects cardiac function. miRNAs are vital in cardiovascular diseases (CVD), such as hypertrophy and heart failure. While miR-21, miR-29, and miR-133a have defined roles, the function of miR-378a in cardiac hypertrophy is not fully understood.

Thesis is embargoed until 31 July 2030.

Date of Award	2025
Original language	English
Awarding Institution	Queen's University Belfast
Supervisor	Qiaozhu Su (Supervisor) & David Grieve (Supervisor)