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 DelhiView Archive Info
Upregulation of miR-23a,27a,24-2 Cluster Induces
Caspase-Dependent and -Independent Apoptosis in
Human Embryonic Kidney Cells
Adlakha, Yogita K.
G1 Genome informatics (General)
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
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.