title: Blockage of miR-92a-3p with locked nucleic acid induces apoptosis and prevents cell proliferation in human acute megakaryoblastic leukemia.
abstract: MicroRNAs (miRNAs) are non-coding RNAs involved in post-transcriptional regulation of gene expression. In many cancers, up- or downregulation of different miRNAs is reported. In acute myeloid leukemia, upregulation of miR-92a-3p was reported in human in vitro studies. We performed blockage of miR-29a-3p in human acute megakaryoblastic leukemia cell line (M-07e) by using locked nucleic acid (LNA) and cell proliferation; apoptosis and necrosis were assessed. At different time points after LNA-anti-miR92a-3p transfection, miR-92a-3p quantitation was assessed by qRT-real-time PCR, MTT assay and annexin/propidium iodide staining were performed. The data were processed using the ANOVA test. At all three time points, the expression of miR-92a-3p was lower in the LNA-anti-miR group compared with the control groups. Cell viability between LNA-Anti-miR and the control group was statistically significant. Blockage of miR-92a-3p was associated with increment of the ratio of apoptotic cells in the LNA-anti-miR group was higher than the other group. The ratio of necrotic cells in the LNA-antimiR group was higher than the other groups. These assessments indicate that miR-92a-3p blockage can decrease the viability of M-07e cells, which is mainly due to induction of apoptosis and necrosis. Our findings could open up a path to a miRNA based therapeutic approach for treatment of acute megakaryoblastic leukemia.
authors.affiliation: Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: M
authors.identifier: http://orcid.org/0000-0002-1538-9034
authors.initials: M
authors.lastname: Sharifi
authors.affiliation: Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: R
authors.initials: R
authors.lastname: Salehi
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D007947:Leukemia, Megakaryoblastic, Acute / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D035683:MicroRNAs / Q000187:drug effects / Q000235:genetics*; D009336:Necrosis; D009841:Oligonucleotides / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
chemical_list: D000970:Antineoplastic Agents; C541874:MIRN92 microRNA, human; D035683:MicroRNAs; D009841:Oligonucleotides; C477371:locked nucleic acid