Potential tumor suppressive function of miR-196b in B-cell lineage acute lymphoblastic leukemia
Potential tumor suppressive function of miR-196b in B-cell lineage acute lymphoblastic leukemia
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DOI：
10.1007/s11010-010-0406-9
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发表时间：
2010-07-01
影响因子：
4.3
通讯作者：
Varma, Neelam
中科院分区：
文献类型：
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作者：
Bhatia, Suman;Kaul, Deepak;Varma, Neelam
考虑到编码microRNA（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B细胞急性淋巴细胞白血病（B-cell ALL）遗传易位特征相关区域附近/区域内的miRNAs。在6个这样鉴定的miRNAs中，发现miR-196 b不仅在EB-3细胞系以及B细胞ALL患者中与在相应对照中发现的相比显著下调，而且还具有下调高表达的c-myc基因的固有能力，这是EB-3细胞在转录和翻译水平上的遗传易位特征的结果。这一现象与所观察到的来源于ALL患者的B细胞中编码miR-196 b和c-myc的表达基因之间的相互关系一致，并且发现c-myc基因是miR-196 b的推定靶点，如生物信息学算法所预测的。c-myc基因的下调伴随着c-myc效应基因hTERT、Bcl-2和AATF的表达降低。基于这些结果，我们首次提出miR-196 b具有下调过度扩增的c-myc基因的固有能力，该基因被认为是导致癌症的常见特征，特别是B细胞ALL。因此，miR-196 b可以被分配具有肿瘤抑制功能，并且可以在为治疗B细胞ALL铺平道路方面具有治疗重要性。
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.