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

• Main Authors: Esa, Ezalia, Hashim, Ariwibawa Kasmani, Mohamed, Elsa Haniffah Mejia, Zakaria, Zubaidah, Abu Hassan, Alifah Nadia, Yusoff, Yuslina Mat, Kamaluddin, Nor Rizan, Rahman, Ahmad Zuhairi Abdul, Chang, Kian-Meng, Mohamed, Rashidah, Subbiah, Indhira, Jamian, Ehram, Ho, Caroline Siew-Ling, Lim, Soo-Min, Lau, Peng-Choon, Pung, Yuh-Fen, Zain, Shamsul Mohd
• Format: Article
• Published: Mary Ann Liebert, Inc 2021
• Subjects: R Medicine; R Medicine (General)
• Online Access: http://eprints.um.edu.my/34598/

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.