Molecular Biology Unit, Department of Experimental Medicine and Biotechnology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India.
Mol Cell Biochem. 2011 Jan;346(1-2):103-16. doi: 10.1007/s11010-010-0597-0. Epub 2010 Oct 6.
Huge data accumulated in last few years have shown that differential expression of candidate miRNAs in normal versus transformed cell provides important insights into the pathogenesis of cancer including leukemias. In our previous report, we have revealed that miR-196b was significantly down-regulated in both EB-3 cells as well as B-cell ALL (acute lymphoblastic leukemia) patients as compared to their respective controls. We have unambiguously proven that miR-196b restoration in EB-3 cells leads to significant down-regulation of c-myc and its effector genes, i.e., human telomerase reverse transcriptase (hTERT), B-cell lymphoma/leukemia-2 (Bcl-2), apoptosis antagonizing transcription factor (AATF), and qualifies for tumor suppressor function in B-cell ALL. Keeping in view these results, the present study was aimed at dissecting the role of miR-196b and other miRNAs present near/within the genomic regions involved in genetic translocations characteristic of ALL in T-cell ALL cell lines and patient samples. We have demonstrated significant down-regulation in the expression of miR-196b in MOLT-4 and T-cell ALL patients with respect to the respective control cells. Transfection experiments revealed that none of the six identified miRNAs were able to knock down the expression of c-myc gene. Interestingly, it was found that miR-196b loses its ability to down-regulate c-myc gene expression in T-cell ALL as a consequence of mutations in target 3'-untranslated region (3'-UTR) of the c-myc gene. Results of the present study revealed that miR-196b becomes non-functional in T-cell ALL as a consequence of mutations in 3'-UTR of c-myc gene in T-cell ALL cellular models.
在过去的几年中积累了大量数据，这些数据表明候选 miRNA 在正常细胞与转化细胞中的差异表达为包括白血病在内的癌症发病机制提供了重要的见解。在我们之前的报告中，我们已经揭示 miR-196b 在 EB-3 细胞以及 B 细胞 ALL（急性淋巴细胞白血病）患者中均显著下调，与各自的对照相比。我们已经明确证明，在 EB-3 细胞中恢复 miR-196b 会导致 c-myc 及其效应基因（即人端粒酶逆转录酶（hTERT）、B 细胞淋巴瘤/白血病-2（Bcl-2）、凋亡拮抗转录因子（AATF））的显著下调，并具有 B 细胞 ALL 中的肿瘤抑制功能。鉴于这些结果，本研究旨在探讨 miR-196b 及其在涉及 ALL 的遗传易位特征的基因组区域内或附近的其他 miRNA 在 T 细胞 ALL 细胞系和患者样本中的作用。我们已经证明，与各自的对照细胞相比，MOLT-4 和 T 细胞 ALL 患者的 miR-196b 表达显著下调。转染实验表明，在这六个鉴定的 miRNA 中，没有一个能够下调 c-myc 基因的表达。有趣的是，发现 miR-196b 在 T 细胞 ALL 中失去了下调 c-myc 基因表达的能力，这是由于 c-myc 基因 3'-非翻译区（3'-UTR）的突变所致。本研究的结果表明，miR-196b 在 T 细胞 ALL 中变得无功能，这是由于 T 细胞 ALL 细胞模型中 c-myc 基因 3'-UTR 的突变所致。
