Inhibition of microRNA miR-92a induces apoptosis and inhibits cell proliferation in human acute promyelocytic leukemia through modulation of p63 expression.
MicroRNAs (miRNAs) are endogenous non-coding RNAs, 19-25 nucleotides in length involved in post-transcriptional regulation of gene expression of great majority of the human protein coding genes. Different aspects of cellular activities like cell growth, proliferation, and differentiation are regulated by miRNAs through their interaction with particular RNA species. In many tumors up or down-regulation of different miRNAs has been reported. Human miR-17-92 gene cluster is located on 13q31.3, rooming several miRNAs including miR-17-5p, miR-17-3p, miR-18, miR-19a, miR-20a and miR-92a. Amplification or overexpression of this cluster has been reported in acute myeloid leukemia, acute lymphoblastic leukemia and several other cancer types. Here, we performed inhibition of miR-92a in an acute promyelocytic leukemia (APL) cell line (HL-60) using locked nucleic acid (LNA) antagomir. In different time points after LNA-anti-miR92a transfection, MTT assay and annexin/propidium iodide staining were performed. These assessments indicate that miR-92a inhibition can extensively decrease the viability of these cells which is mainly due to induction of apoptosis. Western blot analysis of p63 protein also revealed that miR-92a inhibition resulted in p63 expression, hence activation of cellular pathways which are normally controlled by p63 protein are retrieved. These findings could open up a path to the miRNAs based therapeutic approach for treatment of APL.
Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, 81744-176, Isfahan, Iran.
Mohammadreza
M
Sharifi
Rasoul
R
Salehi
Yousof
Y
Gheisari
Mohammad
M
Kazemi
D017209:Apoptosis / Q000235:genetics*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D018922:HL-60 Cells; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics* / Q000378:metabolism; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics*; D009336:Necrosis / Q000235:genetics; D009841:Oligonucleotides / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
C541874:MIRN92 microRNA, human; D035683:MicroRNAs; D009841:Oligonucleotides; C115051:TP63 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C477371:locked nucleic acid