title: Identification and functional characterization of the miRNA-gene regulatory network in chronic myeloid leukemia lineage negative cells.
abstract: Chronic myeloid leukemia (CML) is maintained by leukemic stem cells (LSCs) which are resistant to the existing TKI therapy. Hence a better understanding of the CML LSCs is necessary to eradicate these cells and achieve complete cure. Using the miRNA-gene interaction networks from the CML lin(-) cells we identified a set of up/down-regulated miRNAs and corresponding target genes. Association studies (Pearson correlation) from the miRNA and gene expression data showed that miR-1469 and miR-1972 have significantly higher number of target genes, 75 and 50 respectively. We observed that miR-1972 induces G2-M cell cycle arrest and miR-1469 moderately arrested G1 cell cycle when overexpressed in KCL22 cells. We have earlier shown that a combination of imatinib and JAK inhibitor I can significantly bring down the proliferation of CML lineage negative cells. Here we observed that imatinib and JAK inhibitor I combination restored the expression pattern of the down-regulated miRNAs in primary CML lin(-) cells. Thus effective manipulation of the deregulated miRNAs can restore the miRNA-mRNA networks that can efficiently inhibit CML stem and progenitor cells and alleviate the disease.
authors: Institute of Life Sciences, Nalco Square, Bhubaneswar, Odisha, India.
authors: S
authors: S
authors: Agatheeswaran
authors: Department of Clinical Haematology, SCB Medical College, Cuttack, Odisha, India.
authors: N C
authors: NC
authors: Pattnayak
authors: Institute of Life Sciences, Nalco Square, Bhubaneswar, Odisha, India.
authors: S
authors: S
authors: Chakraborty
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D019070:Cell Lineage / Q000187:drug effects / Q000235:genetics*; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects / Q000235:genetics; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects / Q000235:genetics; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects; D053263:Gene Regulatory Networks / Q000187:drug effects; D006801:Humans; D000068877:Imatinib Mesylate / Q000494:pharmacology / Q000627:therapeutic use; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D020687:cdc25 Phosphatases / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D048868:Adaptor Proteins, Signal Transducing; C082869:CRKL protein; D035683:MicroRNAs; D009687:Nuclear Proteins; D012333:RNA, Messenger; D000068877:Imatinib Mesylate; C517008:CDC25B protein, human; D020687:cdc25 Phosphatases