title: Inducing cell proliferative prevention in human acute promyelocytic leukemia by miR-182 inhibition through modulation of CASP9 expression.
abstract: MicroRNAs (miRNAs) are one class of endogenous non-coding RNAs that involved in post-transcriptional regulation of the gene. MiRNAs through interaction with messenger RNA (mRNA) involved in several biological processes such as cell cycle, differentiation, growth, metabolism, aging and apoptosis. MiRNAs may act as an oncogene or a tumor suppressor via up or down regulation in cancerous cells. MiR-182 located in a miR-183/-96/-182 cluster, this is the highly conserved cluster to have an important role in cancer development and tumorigenesis. Abnormal expression of miR-182 in a variety of human cancers has reported. Oncogenic features of miR-182 confirmed through negative regulation of various tumor suppressor genes. In this study, miR-182 inhibition in acute promyelocytic leukemia (APL) cell line (HL60) was performed by locked nucleic acid (LNA) anti-miR. MTT assay in three-time points 24, 48 and 72h after LNA-anti-miR-182 transfection was performed. Our study demonstrated inhibition of miR-182 can expansively decrease cell proliferation of APL cells. The Western blotting analysis presents that CASP9 expression associated with inhibition of miR-182. CASP9 protein has an important role in the mitochondrial cell death pathway as the initiator of apoptosis. These results can offer a way for inhibition of APL cells proliferates and produce translational medicine based on microgenomics and antisense therapy.
authors.affiliation: Molecular Biology Research Center, Baqiyatallahc University of Medical Sciences, Tehran, Iran. Electronic address: fasihi.m@gmail.com.
authors.forename: Mahdi
authors.initials: M
authors.lastname: Fasihi-Ramandi
authors.affiliation: Molecular Biology Research Center, Baqiyatallahc University of Medical Sciences, Tehran, Iran. Electronic address: a_moridnia@med.mui.ac.ir.
authors.forename: Abbas
authors.initials: A
authors.lastname: Moridnia
authors.affiliation: Molecular Biology Research Center, Baqiyatallahc University of Medical Sciences, Tehran, Iran. Electronic address: najafi74@yahoo.com.
authors.forename: Ali
authors.initials: A
authors.lastname: Najafi
authors.affiliation: Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Science, Isfahan, 81744-176, Iran. Electronic address: mo_sharifi@med.mui.ac.ir.
authors.forename: Mohammadreza
authors.initials: M
authors.lastname: Sharifi
mesh_terms: D017209:Apoptosis / Q000235:genetics; D053453:Caspase 9 / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D015536:Down-Regulation / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics; D016147:Genes, Tumor Suppressor / Q000502:physiology; D018922:HL-60 Cells; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D009841:Oligonucleotides / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D014162:Transfection / Q000379:methods
chemical_list: D035683:MicroRNAs; C538984:Mirn182 microRNA, human; D009841:Oligonucleotides; D012333:RNA, Messenger; C477371:locked nucleic acid; C506433:CASP9 protein, human; D053453:Caspase 9
keywords: Acute promyelocytic leukemia; CASP9; LNA; MiR-182