NDLI: Functional genomics of tumor suppressor miR-196b in T-cell acute lymphoblastic leukemia

Content Provider	Springer Nature Link
Author	Bhatia, Suman Kaul, Deepak Varma, Neelam
Copyright Year	2010
Abstract	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.
Starting Page	103
Ending Page	116
Page Count	14
File Format	PDF
ISSN	03008177
Journal	Molecular and Cellular Biochemistry
Volume Number	346
Issue Number	1-2
e-ISSN	15734919
Language	English
Publisher	Springer US
Publisher Date	2010-10-06
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	miRNAs Translocations c-myc T-cell acute lymphoblastic leukemia 3′-Untranslated region Cardiology Oncology Medical Biochemistry Biochemistry
Content Type	Text
Resource Type	Article
Subject	Cell Biology Medicine Clinical Biochemistry Molecular Biology

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