Upregulation of miR-23a,27a,24-2 Cluster Induces Caspase-Dependent and -Independent Apoptosis in Human Embryonic Kidney Cells
IR@IGIB: CSIR-Institute of Genomics & Integrative Biology, New Delhi
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Title |
Upregulation of miR-23a,27a,24-2 Cluster Induces
Caspase-Dependent and -Independent Apoptosis in
Human Embryonic Kidney Cells
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Creator |
Chhabra, Ravindresh
Adlakha, Yogita K. Hariharan, Manoj Scaria, Vinod Saini, Neeru |
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Subject |
G1 Genome informatics (General)
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Description |
miRNAs have emerged as important players in the regulation of gene expression and their deregulation is a common
feature in a variety of diseases, especially cancer. Currently, many efforts are focused on studying miRNA expression
patterns, as well as miRNA target validation. Here, we show that the over expression of miR-23a,27a,24-2 cluster in
HEK293T cells induces apoptosis by caspase-dependent as well as caspase-independent pathway as proved by the annexin
assay, caspase activation, release of cytochrome-c and AIF (apoptosis inducing factor) from mitochondria. Furthermore, the
over expressed cluster modulates the expression of a number of genes involved in apoptosis including FADD (Fas
Associated protein with Death Domain). Bioinformatically, FADD is predicted to be the target of hsa-miR-27a and
interestingly, FADD protein was found to be up regulated consistent with very less expression of hsa-miR-27a in HEK293T
cells. This effect was direct, as hsa-miR-27a negatively regulated the expression of FADD 39UTR based reporter construct.
Moreover, we also showed that over expression of miR-23a,27a,24-2 sensitized HEK293T cells to TNF-a cytotoxicity. Taken
together, our study demonstrates that enhanced TNF-a induced apoptosis in HEK293T cells by over expression of miR-
23a,27a,24-2 cluster provides new insights in the development of novel therapeutics for cancer
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Date |
2009-06-09
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Type |
Article
PeerReviewed |
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Format |
application/pdf
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Identifier |
http://openaccess.igib.res.in/98/1/19513126.pdf
Chhabra, Ravindresh and Adlakha, Yogita K. and Hariharan, Manoj and Scaria, Vinod and Saini, Neeru (2009) Upregulation of miR-23a,27a,24-2 Cluster Induces Caspase-Dependent and -Independent Apoptosis in Human Embryonic Kidney Cells. PubMed, 4 (6). e5848. |
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Relation |
http://openaccess.igib.res.in/98/
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