title: Integrative computational in-depth analysis of dysregulated miRNA-mRNA interactions in drug-resistant pediatric acute lymphoblastic leukemia cells: an attempt to obtain new potential gene-miRNA pathways involved in response to treatment.
abstract: Acute lymphoblastic leukemia (ALL) is the major neoplasia type among children. Despite the tremendous success of current treatment strategies, drug resistance still remains a major cause of chemotherapy failure and relapse in pediatric patients. Overwhelming evidence illustrates that microRNAs (miRNAs) act as post-transcriptional regulators of drug-resistance-related genes. The current study was aimed at how dysregulated miRNA-mRNA-signaling pathway interaction networks mediate resistance to four commonly used chemotherapy agents in pediatric ALL, including asparaginase, daunorubicin, prednisolone, and vincristine. Using public expression microarray datasets, a holistic in silico approach was utilized to investigate candidate drug resistance miRNA-mRNA-signaling pathway interaction networks in pediatric ALL. Our systems biology approach nominated significant drug resistance and cross-resistance miRNAs, mRNAs, and cell signaling pathways based on anti-correlative relationship between miRNA and mRNA expression pattern. To sum up, our systemic analysis disclosed either a new potential role of miRNAs, or a possible mechanism of cellular drug resistance, in chemotherapy resistance of pediatric ALL. The current study may shed light on predicting drug response and overcoming drug resistance in childhood ALL for subsequent generations of chemotherapies.
authors.affiliation: Division of Cell and Molecular Biology, Department of Biology, Faculty of Science, University of Isfahan, Hezar Jarib Street, 8174673441, Isfahan, Iran.
authors.forename: Hamzeh
authors.initials: H
authors.lastname: Mesrian Tanha
authors.affiliation: Division of Genetics, Department of Biology, Faculty of Science, University of Isfahan, Isfahan, Iran.
authors.forename: Marjan
authors.initials: M
authors.lastname: Mojtabavi Naeini
authors.affiliation: Division of Cell and Molecular Biology, Department of Biology, Faculty of Science, University of Isfahan, Hezar Jarib Street, 8174673441, Isfahan, Iran. rahgozar@sci.ui.ac.ir.
authors.forename: Soheila
authors.initials: S
authors.lastname: Rahgozar
authors.affiliation: Department of Pediatric Hematology Oncology, Sayed Al-Shohada Hospital, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Moafi
authors.affiliation: Division of Cell and Molecular Biology, Department of Biology, Faculty of Science, University of Isfahan, Hezar Jarib Street, 8174673441, Isfahan, Iran.
authors.forename: Mohammad Amin
authors.initials: MA
authors.lastname: Honardoost
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D035683:MicroRNAs; D012333:RNA, Messenger
keywords: Acute lymphoblastic leukemia; Drug resistance; Signaling pathway; Therapeutic targets; miRNA