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Upregulation of miR-23a∼27a∼24-2 Cluster Induces Caspase-Dependent and -Independent Apoptosis in Human Embryonic Kidney Cells
被引:128
作者:
Chhabra, Ravindresh
Adlakha, Yogita K.
Hariharan, Manoj
Scaria, Vinod
Saini, Neeru
机构:
[1] Institute of Genomics and Integrative Biology, Delhi
来源:
PLOS ONE
|
2009年
/
4卷
/
06期
关键词:
D O I:
10.1371/journal.pone.0005848
中图分类号:
O [数理科学和化学];
P [天文学、地球科学];
Q [生物科学];
N [自然科学总论];
学科分类号:
07 ;
0710 ;
09 ;
摘要:
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 similar to 27a similar to 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 similar to 27a similar to 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 similar to 27a similar to 24-2 cluster provides new insights in the development of novel therapeutics for cancer.
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