Upregulation of miR-23a-27a-24-2 cluster induces caspase-dependent and -independent apoptosis in human embryonic kidney cells.

• Main Authors: Ravindresh Chhabra, Yogita K Adlakha, Manoj Hariharan, Vinod Scaria, Neeru Saini
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2009-06-01
• Series: PLoS ONE
• Online Access: http://europepmc.org/articles/PMC2689653?pdf=render

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 approximately 27a approximately 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 3'UTR based reporter construct. Moreover, we also showed that over expression of miR-23a approximately 27a approximately 24-2 sensitized HEK293T cells to TNF-alpha cytotoxicity. Taken together, our study demonstrates that enhanced TNF-alpha induced apoptosis in HEK293T cells by over expression of miR-23a approximately 27a approximately 24-2 cluster provides new insights in the development of novel therapeutics for cancer.