Tumor suppressive function of microRNA-192 in acute lymphoblastic leukemia.

Mahtab Sayadi,Soheila Ajdary,Shahrbano Rostami,Fatemeh Nadali,Mahdi Edalati Fahtabad

doi:10.17305/bjbms.2017.1921

Abstract

Non-coding RNAs play a critical role in gene regulation in cancer cells. Reduced expression of microRNA-192 (miR-192) has been detected in many cancers. In this study, we investigated the role of miR-192 in cell proliferation and cell cycle control in NALM-6 cell line, a model of acute lymphoblastic leukemia (ALL). Cell cycle analysis by DNA content using propidium iodide staining and cell apoptosis analysis using Annexin V assay were carried out. Cell proliferation changes were monitored using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. In addition, the relative changes in P53, BAX, CASP3, and BCL-2 gene expression were determined by quantitative reverse transcription PCR. Overexpression of miR-192 resulted in cell proliferation arrest in ALL cells. After 72 and 96 hours of transduction, apoptosis was significantly increased in the cells transduced with miR-192-overexpressing virus compared with control cells. The expression of P53, BAX, and CASP3 increased after 48 hours of transduction in miR-192-overexpressing cells, but no change was observed in BCL-2 expression. The G0/S and G1/S ratio changed to 7.5 and 4.5, respectively, in the cells overexpressing miR-192 compared with controls. The results of our study suggest, for the first time, tumor suppressive effects of miR-192 in ALL cells.

Highlights

IntroductionMicroRNAs (miRNAs) are small, endogenous, non-coding single-stranded RNAs approximately 20-25 nucleotides long that play key roles in post-transcriptional regulation of gene expression in multicellular organisms [1]
MicroRNAs are small, endogenous, non-coding single-stranded RNAs approximately 20-25 nucleotides long that play key roles in post-transcriptional regulation of gene expression in multicellular organisms [1]. These small sequences usually bind to the 3′-untranslated region (3′-UTR) of the target mRNA through imperfect base-pairing, and either block translation or promote degradation of the target mRNA [2]
MiR-192 was downregulated in colorectal cancer and hematological disorders, as well as in lymphoblastic leukemia (ALL) where it was associated with poor prognosis (Supplemental Table 1) [11,12]

Summary

Introduction

MicroRNAs (miRNAs) are small, endogenous, non-coding single-stranded RNAs approximately 20-25 nucleotides long that play key roles in post-transcriptional regulation of gene expression in multicellular organisms [1]. These small sequences usually bind to the 3′-untranslated region (3′-UTR) of the target mRNA through imperfect base-pairing, and either block translation or promote degradation of the target mRNA [2]. Based on the function of the target genes, miRNAs can act as oncogenic (oncomiR) or tumor suppressive, and play a critical role in the carcinogenesis due to changes in the expression of regulatory proteins [3,4,5]. The TP53 gene is a direct transcriptional target of miR-192, which contributes to the tumor suppressive role of this miRNA. The TP53 gene is a direct transcriptional target of miR-192, which contributes to the tumor suppressive role of this miRNA. miR-192 affects the regulation of cell cycle and proliferation by regulating the TP53 expression [11]

Methods

Results

Conclusion