Integrating microRNA and mRNA expression profiles of acute promyelocytic leukemia cells to explore the occurrence mechanisms of differentiation syndrome.

Abstract	The pathogenesis of therapy-induced differentiation syndrome (DS) in patients with acute promyelocytic leukemia (APL) remains unclear. In this study, mRNA and microRNA (miRNA) expression profiling of peripheral blood APL cells from patients complicated with vs. without DS were integratively analyzed to explore the mechanisms underlying arsenic trioxide treatment-associated DS. By integrating the differentially expressed data with the data of differentially expressed microRNAs and their computationally predicted target genes, as well as the data of transcription factors and differentially expressed target microRNAs obtained from a literature search, a DS-related genetic regulatory network was constructed. Then using an EAGLE algorithm in clusterViz, the network was subdivided into 10 modules. Using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database the modules were annotated functionally, and three functionally active modules were recognized. The further in-depth analyses on the annotated functions of the three modules and the expression and roles of the related genes revealed that proliferation, differentiation, apoptosis and infiltration capability of APL cells might play important roles in the DS pathogenesis. The results could improve our understanding of DS pathogenesis from a more overall perspective, and could provide new clues for future research.
Authors	Yingmei Zhang, Jinxiao Hou, Fei Ge, Fenglin Cao, Haitao Li, Ping Wang, Mengyuan Xu, Peng Song, Xiaoxia Li, Shuye Wang, Jinmei Li, Xueying Han, Yanhong Zhao, Yanhua Su, Yinghua Li, Shengjin Fan, Limin Li, Jin Zhou
Journal	Oncotarget (Oncotarget) Vol. 7 Issue 45 Pg. 73509-73524 (Nov 08 2016) ISSN: 1949-2553 [Electronic] United States
PMID	27634874 (Publication Type: Journal Article)
Chemical References	MicroRNAs RNA, Messenger
Topics	Cell Differentiation (genetics) Cell Line, Tumor Computational Biology (methods) Gene Expression Profiling Gene Expression Regulation, Leukemic Gene Regulatory Networks Humans Leukemia, Promyelocytic, Acute (genetics, metabolism, pathology) MicroRNAs (genetics) Molecular Sequence Annotation RNA, Messenger (genetics) Reproducibility of Results Transcriptome

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