Molecular Biology Unit, Department of Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.
Mol Cell Biochem. 2010 Jul;340(1-2):97-106. doi: 10.1007/s11010-010-0406-9. Epub 2010 Feb 21.
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.
鉴于编码 microRNAs (miRNAs) 的基因已被发现定位于易发生遗传易位的染色体区域，本研究旨在鉴定和表征存在于涉及 B 细胞急性淋巴细胞白血病 (B-cell ALL) 特征性遗传易位区域附近/内的 miRNAs。在鉴定出的六个 miRNA 中，miR-196b 不仅在 EB-3 细胞系和 B-cell ALL 患者中均明显下调，与相应对照相比，而且还具有内在能力下调高度表达的 c-myc 基因，这是 EB-3 细胞遗传易位的特征，在转录和翻译水平上均如此。这一现象与从 ALL 患者来源的 B 细胞中观察到的 miR-196b 和 c-myc 编码基因表达之间的相互关系一致，并且 c-myc 基因被发现是 miR-196b 的推定靶标，这是通过生物信息学算法预测的。此外，c-myc 基因的下调伴随着编码 hTERT、Bcl-2 和 AATF 的 c-myc 效应基因的表达下调。基于这些结果，我们首次提出 miR-196b 具有内在能力下调被认为是导致癌症的一般特征的过扩增 c-myc 基因。因此，miR-196b 可以被赋予肿瘤抑制功能，并在为治疗 B 细胞 ALL 铺平道路方面具有治疗意义。
