1. Construction of a microRNA-mRNA Regulatory Network in De Novo Cytogenetically Normal Acute Myeloid Leukemia Patients.
- Author
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Esa E, Hashim AK, Mohamed EHM, Zakaria Z, Abu Hassan AN, Mat Yusoff Y, Kamaluddin NR, Abdul Rahman AZ, Chang KM, Mohamed R, Subbiah I, Jamian E, Ho CS, Lim SM, Lau PC, Pung YF, and Zain SM
- Subjects
- Adult, Aged, Cytogenetic Analysis methods, Female, Gene Expression Profiling methods, Gene Regulatory Networks genetics, Humans, Malaysia, Male, Middle Aged, Leukemia, Myeloid, Acute genetics, MicroRNAs genetics, RNA, Messenger genetics
- Abstract
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.
- Published
- 2021
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