Upregulation of miR-23a,27a,24-2 Cluster Induces Caspase-Dependent and -Independent Apoptosis in Human Embryonic Kidney Cells

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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Abstract

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

Item Type: Article
Subjects: G Genome informatics > G1 Genome informatics (General)
Divisions: Faculty of Genome informatics and Structural Biology > School of Genome informatics
Depositing User: Raghu MV
Date Deposited: 27 Dec 2011 10:02
Last Modified: 28 Feb 2012 05:48
URI: http://openaccess.igib.res.in/id/eprint/98

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