Mir-Let-7i-5p As A Novel Regulator of MYC Gene Expression in Acute Myeloid Leukaemia

Ezalia  Esa; Wan Muhammad Farhan Syafiq  Wan Mohd Nor; Elsa Haniffah  Mejia Mohamed; Wei-Yue Lim; Zubaidah  Zakaria; Yuslina  Mat Yusoff; Ivyna Pau Ni Bong; Yuh-Fen Pung; Noor Atiqah  Fakharuzi; Shamsul Mohd Zain

doi:10.55230/mabjournal.v54i4.3590

Authors

Ezalia Esa Haematology Unit, Cancer Research Centre, Institute for Medical Research, Jalan Pahang, Kuala Lumpur, Malaysia
Wan Muhammad Farhan Syafiq Wan Mohd Nor Department of Pharmacology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia
Elsa Haniffah Mejia Mohamed Department of Pharmacology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia
Wei-Yue Lim Department of Pharmacology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia
Zubaidah Zakaria Haematology Unit, Cancer Research Centre, Institute for Medical Research, Jalan Pahang, Kuala Lumpur, Malaysia
Yuslina Mat Yusoff Haematology Unit, Cancer Research Centre, Institute for Medical Research, Jalan Pahang, Kuala Lumpur, Malaysia
Ivyna Pau Ni Bong Haematology Unit, Cancer Research Centre, Institute for Medical Research, Jalan Pahang, Kuala Lumpur, Malaysia
Yuh-Fen Pung Division of Biomedical Science, School of Pharmacy, University of Nottingham Malaysia, Semenyih, Selangor, Malaysia
Noor Atiqah Fakharuzi Haematology Unit, Cancer Research Centre, Institute for Medical Research, Jalan Pahang, Kuala Lumpur, Malaysia
Shamsul Mohd Zain
shamsul@um.edu.my
Department of Pharmacology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia

Keywords:

Cancer, Molecular, cell culture, biology, leukaemia

Abstract

Acute myeloid leukaemia (AML) is a severe bone marrow malignancy with a high mortality rate. Recent advancements in high-throughput technology and bioinformatics have facilitated the identification of microRNAs (miRNAs) involved in the pathogenesis of AML. This study aimed to investigate the potential role of MicroRNA-let-7i-5p (miR-let-7i-5p) in the progression of AML. MiR-let-7 family has been widely utilised as a tumour inhibitor, suppressing its expression in several types of human cancer. Hence, dysregulation of miR-let-7i-5p is critical to cancer progression. However, the role of miR-let-7i-5p in AML remains unclear. Using the Gene Expression Omnibus (GEO) database, the expression of miR-let-7i-5p in AML patients was investigated. The role of miR-let-7i-5p and its potential target genes in AML was examined using bioinformatic tools. Subsequently, the effect of miR-let-7i-5p was assessed through transfection, followed by the analysis of target gene expression using RT-qPCR. Further investigations employed the MTT and cell cycle assays on the effects of miR-let-7i-5p on AML cell proliferation and cell cycle. According to the GEO database, miR-let-7i-5p was significantly downregulated in AML patients compared to controls. AML development has been associated with miR-let-7i-5p by KEGG pathway analysis. Bioinformatics suggested that miR-let-7i-5p targets MYC in AML cells. Transfection of miR-let-7i-5p into AML cell lines decreased MYC expression, suggesting MYC regulates AML progression. However, MTT and cell cycle assays showed no significant effect of miR-let-7i-5p on AML cell proliferation and cell cycle, indicating the potential involvement of miR-let-7i-5p in alternative pathways in AML pathogenesis. The study highlights the potential significance of miR-let-7i-5p in regulating AML progression.

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