Potential tumor suppressive function of miR-196b in B-cell lineage acute lymphoblastic leukemia.
Keeping in view the fact that genes coding microRNAs (miRNAs) have been found to be localized in chromosomal regions susceptible to genetic translocations, this study was addressed to identify and characterize the miRNAs that are present near/within the regions involved in genetic translocations characteristic of B-cell acute lymphoblastic leukemia (B-cell ALL). Out of six such identified miRNAs miR-196b was not only found to be significantly down-regulated in both EB-3 cell line as well as B-cell ALL patients as compared to that found in the corresponding controls, but also had the inherent capacity to down-regulate the highly expressed c-myc gene, a consequence of genetic translocation characteristic of EB-3 cells at both transcriptional and translational level. This phenomenon was in conformity with the observed reciprocal relationship between the expressed genes coding for miR-196b and c-myc in B-cells derived from ALL patients as well as c-myc gene was found to be a putative target of miR-196b as predicted by bioinformatic algorithms. Also down-regulation of c-myc gene was accompanied by decreased expressions of c-myc effector genes coding for hTERT, Bcl-2, and AATF. Based upon these results, we propose for the first time that miR-196b has the inherent capacity to down-regulate the overamplified c-myc gene recognized as a common pathognomonic feature leading to cancer in general and B-cell ALL in particular. Hence miR-196b can be assigned with the tumor suppressor function and can be of therapeutic importance in paving the way toward the treatment of B-cell ALL.
Bhatia
Suman
S
Molecular Biology Unit, Department of Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.
Kaul
Deepak
D
Varma
Neelam
N
D000465:Algorithms; D017209:Apoptosis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019295:Computational Biology; D015536:Down-Regulation; D015973:Gene Expression Regulation, Leukemic; D016147:Genes, Tumor Suppressor; D006801:Humans; D035683:MicroRNAs / Q000378:metabolism*; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D019098:Telomerase / Q000235:genetics; D014158:Transcription, Genetic; D014162:Transfection
C402637:AATF protein, human; D051017:Apoptosis Regulatory Proteins; C542543:MIRN196 microRNA, human; C489427:MYC protein, human; D035683:MicroRNAs; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D012097:Repressor Proteins; C509186:TERT protein, human; D019098:Telomerase