Novel insights into the role of long non-coding RNA MIAT in leukaemia

Ostini, Alessia

Abstract

lncRNAs are key regulators of various cellular processes, playing significant roles in both healthy and malignant contexts, and actively contributing to carcinogenesis and cell fate determination. This study investigates the role of Myocardial Infarction Associated Transcript (MIAT) in leukaemia.

Silencing MIAT using siRNA significantly reduces both short- and long-term survival and increases the apoptotic rate in leukemic cells. Gene expression analysis revealed that reduced MIAT levels are associated with significant dysregulation of major oncogenes and tumour suppressor genes, as well as a wide array of genes involved in cell cycle regulation. Further analysis highlighted MIAT's potential involvement in major cancer signalling pathways, including the druggable MAPK and TGF-β pathways.

This study indicates that MIAT plays a critical role in gene regulation. MIAT silencing led to perturbations in miRNA expression and alters gene expression both at transcription sites and distant chromosomal loci, indicating that MIAT operates through both trans and cis-acting mechanisms. MIAT downregulation also affects the abundance of splice variant transcripts of several oncogenes and tumour suppressor genes, highlighting its significant role in the splicing machinery.

Another novel finding of this study is the high expression of the MIAT 3’end region following MIAT downregulation. 3’end upregulation leads to decreased MIAT levels, reduced short-term cell survival, increased apoptotic rate, and dysregulation of key oncogenes and tumour suppressors, closely mimicking the effects of siRNA-mediated MIAT silencing. These results suggest that the 3’end of MIAT plays a crucial role in regulating MIAT stability, and its loss may be linked to increased MIAT expression in cancer. The current study highlights the key oncogenic role of MIAT in leukaemia and its involvement in the dysregulation of multiple oncogenes and tumour suppressor genes. Future research should investigate the potential of MIAT as a target for cell and gene therapy and as a prognostic marker.

Citation

Ostini, A. (2025). Novel insights into the role of long non-coding RNA MIAT in leukaemia. (Thesis). Keele University. https://keele-repository.worktribe.com/output/1280075

• Thesis Type: Thesis
• Online Publication Date: Jun 26, 2025
• Deposit Date: Jun 18, 2025
• Publicly Available Date: Jun 27, 2025
• Public URL: https://keele-repository.worktribe.com/output/1280075
• Award Date: 2025-06