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

PLoS One. 2009 Jun 9;4(6):e5848. doi: 10.1371/journal.pone.0005848.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Caspases / metabolism*
  • Cell Line
  • Cell Line, Tumor
  • Cytochromes c / metabolism
  • Gene Expression Regulation, Developmental*
  • Humans
  • Kidney / cytology
  • Kidney / embryology*
  • Membrane Potentials
  • MicroRNAs / biosynthesis*
  • MicroRNAs / metabolism*
  • Rats
  • Tumor Necrosis Factor-alpha / metabolism
  • Up-Regulation


  • MIRN24 microRNA, human
  • MIRN27 microRNA, human
  • MicroRNAs
  • Tumor Necrosis Factor-alpha
  • Cytochromes c
  • Caspases