Construction of a microRNA-mRNA regulatory network in de novo cytogenetically normal acute myeloid leukemia patients

Esa, Ezalia and Hashim, Ariwibawa Kasmani and Mohamed, Elsa Haniffah Mejia and Zakaria, Zubaidah and Abu Hassan, Alifah Nadia and Yusoff, Yuslina Mat and Kamaluddin, Nor Rizan and Rahman, Ahmad Zuhairi Abdul and Chang, Kian-Meng and Mohamed, Rashidah and Subbiah, Indhira and Jamian, Ehram and Ho, Caroline Siew-Ling and Lim, Soo-Min and Lau, Peng-Choon and Pung, Yuh-Fen and Zain, Shamsul Mohd (2021) Construction of a microRNA-mRNA regulatory network in de novo cytogenetically normal acute myeloid leukemia patients. Genetic Testing And Molecular Biomarkers, 25 (3). pp. 199-210. ISSN 1945-0265, DOI

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Background: The association between dysregulated microRNAs (miRNAs) and acute myeloid leukemia (AML) is well known. However, our understanding of the regulatory role of miRNAs in the cytogenetically normal AML (CN-AML) subtype pathway is still poor. The current study integrated miRNA and mRNA profiles to explore novel miRNA-mRNA interactions that affect the regulatory patterns of de novo CN-AML. Methods: We utilized a multiplexed nanoString nCounter platform to profile both miRNAs and mRNAs using similar sets of patient samples (n = 24). Correlations were assessed, and an miRNA-mRNA network was constructed. The underlying biological functions of the mRNAs were predicted by gene enrichment. Finally, the interacting pairs were assessed using TargetScan and microT-CDS. We identified 637 significant negative correlations (false discovery rate <0.05). Results: Network analysis revealed a cluster of 12 miRNAs representing the majority of mRNA targets. Within the cluster, five miRNAs (miR-495-3p, miR-185-5p, let-7i-5p, miR-409-3p, and miR-127-3p) were posited to play a pivotal role in the regulation of CN-AML, as they are associated with the negative regulation of myeloid leukocyte differentiation, negative regulation of myeloid cell differentiation, and positive regulation of hematopoiesis. Conclusion: Three novel interactions in CN-AML were predicted as let-7i-5p:HOXA9, miR-495-3p:PIK3R1, and miR-495-3p:CDK6 may be responsible for regulating myeloid cell differentiation in CN-AML.

Item Type: Article
Funders: Fundamental Research Grant Scheme [FP027-2018A]
Uncontrolled Keywords: acute myeloid leukemia; hematological malignancies; miRNA; mRNA; interaction
Subjects: R Medicine
R Medicine > R Medicine (General)
Divisions: Faculty of Medicine
Depositing User: Ms Zaharah Ramly
Date Deposited: 01 Jun 2022 07:39
Last Modified: 01 Jun 2022 07:39

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