Upregulation of miR-23a∼27a∼24-2 Cluster Induces Caspase-Dependent and -Independent Apoptosis in Human Embryonic Kidney CellsReportar como inadecuado




Upregulation of miR-23a∼27a∼24-2 Cluster Induces Caspase-Dependent and -Independent Apoptosis in Human Embryonic Kidney Cells - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

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 3′UTR based reporter construct. Moreover, we also showed that over expression of miR-23a∼27a∼24-2 sensitized HEK293T cells to TNF-α cytotoxicity. Taken together, our study demonstrates that enhanced TNF-α 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.



Autor: Ravindresh Chhabra , Yogita K. Adlakha , Manoj Hariharan, Vinod Scaria, Neeru Saini

Fuente: http://plos.srce.hr/



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