Construction of a microRNA-mRNA regulatory network in de novo cytogenetically normal acute myeloid leukemia patients
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 profil...
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my.um.eprints.345982022-06-01T07:39:15Z http://eprints.um.edu.my/34598/ Construction of a microRNA-mRNA regulatory network in de novo cytogenetically normal acute myeloid leukemia patients 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 R Medicine R Medicine (General) 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. Mary Ann Liebert, Inc 2021-03 Article PeerReviewed 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 https://doi.org/10.1089/gtmb.2020.0182 <https://doi.org/10.1089/gtmb.2020.0182>. 10.1089/gtmb.2020.0182 |
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R Medicine R Medicine (General) 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 Construction of a microRNA-mRNA regulatory network in de novo cytogenetically normal acute myeloid leukemia patients |
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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. |
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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 |
author_facet |
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 |
author_sort |
Esa, Ezalia |
title |
Construction of a microRNA-mRNA regulatory network in de novo cytogenetically normal acute myeloid leukemia patients |
title_short |
Construction of a microRNA-mRNA regulatory network in de novo cytogenetically normal acute myeloid leukemia patients |
title_full |
Construction of a microRNA-mRNA regulatory network in de novo cytogenetically normal acute myeloid leukemia patients |
title_fullStr |
Construction of a microRNA-mRNA regulatory network in de novo cytogenetically normal acute myeloid leukemia patients |
title_full_unstemmed |
Construction of a microRNA-mRNA regulatory network in de novo cytogenetically normal acute myeloid leukemia patients |
title_sort |
construction of a microrna-mrna regulatory network in de novo cytogenetically normal acute myeloid leukemia patients |
publisher |
Mary Ann Liebert, Inc |
publishDate |
2021 |
url |
http://eprints.um.edu.my/34598/ |
_version_ |
1735409615887138816 |
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13.211869 |