作者：WANG; Long; LI; Xiao-xuan; LIU; Sha; Y...dmagacutemyeloidleukemiadifferentiationlncrnamirnacircrna
摘要：OBJECTIVE To elucidate the underlying mechanism of DMAG in proliferation inhibition and differentia⁃tion induction on acute myeloid leukemia(AML)cell line HEL.METHODS Through CCK8 assay and colony-formation assay to detect the anti-proliferative ability of DMAG on HEL cells.Cell morphological observation(including Giemsa staining assay)and flow cytometry detecting the expression of CD41/CD42b and DNA ploidy detection were performed to identify the effect of DMAG on differentiation of HEL cells.Whole-transcriptome sequencing was taken to investigate the potential molecular mechanism of anti-AML effect of DMAG.Gene Ontology(GO)and KEGG pathway analyses were performed to evaluate molecular processes and biological pathways associated with di ff erentially expressed lncRNA,mRNA,miRNA and circRNA induced by DMAG.Co-expression network analysis was implemented to characterize the differentially expressed lncRNAs,mRNAs,miRNAs and cicrRNAs induced by DMAG.RT-qPCR was used to verify the reliability of the whole-transcriptome sequencing data.RESULTS DMAG not only significantly inhibited the prolifera⁃tion of HEL cells,but also induced the differentiation of HEL cells to megakaryocytes.Whole-transcriptome sequencing showed that a total of 595 lncRNAs,64 miRNAs,4030 mRNAs and 35 circRNAs were remarkably differentially expressed during DMAG induced differentiation of HEL cells.GO and KEGG pathway analyses revealed that those dif⁃ferentially expressed non-coding RNAs were mainly involved in biological processes as diverse as metabolic pathway,apoptosis and cell cycle.Co-expression network analysis indicated that the lncRNA-miRNA-mRNA co-expression network consisted of 40 lncRNAs and 33 miRNAs and 81 mRNAs.Meanwhile,24 circRNA,22 miRNA and 65 mRNAs partook in the construction of circRNA-miRNA-mRNA co-expression network.CONCLUSION DMAG may act as a potent differenti⁃ation inducer of AML cells.
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