title: miRNA-301a induces apoptosis of chronic myelogenous leukemia cells by directly targeting TIMP2/ERK1/2 and AKT pathways.
abstract: We investigated the biological functions and mechanism of miRNA‑301a on apoptosis in chronic myelogenous leukemia (CML). The expression of miRNA‑301a in patient with CML cells was higher than the expression of normal patients. Overall survival (OS) of chronic granulocytic leukemia cell patient with low miRNA‑301 expression was superior to that of CML patient with high miRNA‑301 expression. Moreover, the upregulation of miRNA‑301a increased cell proliferation, inhibited apoptosis and caspase-3 and -9 activity of K562 cells. Next, the upregulation of miRNA‑301a suppressed Bax/Bcl-2 rate and TIMP2 protein expression, increased phosphorylation-ERK1/2 and decreased phosphorylation-AKT protein expression of K562 cells. Furthermore, si‑TIMP2 expression enhanced the upregulation of miRNA‑301a on the promotion of cell proliferation, inhibition of apoptosis and caspase-3 and -9 activity, suppression of Bax/Bcl-2 rate, increasing phosphorylation-ERK1/2 and decreasing phosphorylation-AKT protein expression of K562 cells. Taken together, our results clearly suggested that miRNA‑301a induces apoptosis of CML cells by directly targeting the TIMP2/ERK1/2 and AKT pathways.
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Xianbao
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Ling
authors.initials: L
authors.lastname: Qi
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Gangping
authors.initials: G
authors.lastname: Yang
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Rongyan
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Jia
authors.initials: J
authors.lastname: Rao
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Dexiang
authors.initials: D
authors.lastname: Ji
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Ruibin
authors.initials: R
authors.lastname: Huang
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Guoan
authors.initials: G
authors.lastname: Chen
mesh_terms: D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D016022:Case-Control Studies; D049109:Cell Proliferation; D005434:Flow Cytometry; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D035683:MicroRNAs / Q000235:genetics*; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D009367:Neoplasm Staging; D010766:Phosphorylation; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; C550735:MIRN301A microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; C560823:TIMP2 protein, human; D019716:Tissue Inhibitor of Metalloproteinase-2; D051057:Proto-Oncogene Proteins c-akt; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3