“…For instance, PTEN has been proven to be a target of miR-221/-222. Knockout of these miRNAs results in increased PTEN levels, which in turn lead to suppressed Akt activity and increased apoptosis, and most importantly, to enhanced radiosensitivity in various cancer cell lines (57). These results are in agreement with observations by other authors reporting studies using gastric (58) and colorectal cancer cell lines (54).…”
“…For instance, PTEN has been proven to be a target of miR-221/-222. Knockout of these miRNAs results in increased PTEN levels, which in turn lead to suppressed Akt activity and increased apoptosis, and most importantly, to enhanced radiosensitivity in various cancer cell lines (57). These results are in agreement with observations by other authors reporting studies using gastric (58) and colorectal cancer cell lines (54).…”
“…We found more than 1000 APE1-bound RNA among which many ncRNAs and notably pri-miRNAs that are directly bound by APE1 in cancer cells. In particular, we showed that APE1 endonuclease activity over pri-miR-221/222 mediates the regulation of the tumor suppressor PTEN, a known target of these miRNAs [97]. Moreover, we evidenced, for the first time, that APE1 associates with the Drosha microprocessor complex during oxidative stress suggesting a possible contribution of APE1 in RNA-decay pathways controlling miRNAs precursors stability in the genotoxic cell response.…”
Section: Ber Enzymes and Mirna Regulation: A New Paradigm In Gene Expmentioning
“…miRNA studies have started to expand our understanding about the fact that PTEN is negatively regulated by miR-221/miR-222. Therefore targeted inhibition of miR-221/ miR-222 is effective in enhancing radio-sensitivity (Zhang et al, 2011).…”
Increasingly it is being realized that despite considerable advancements in therapeutic interventions related to treatment of cancer, satisfactory results are still difficult to achieve. Rapidly accumulating evidence has started to shed light on the fact that cancer cells escape from death via constitutive activation of pro-survival signaling cascades. Cell biology and genetics have extensively enhanced our current understanding of the molecular mechanisms that underlie loss of apoptosis in cancer cells. This review is focused on ionizing radiation mediated restoration of TRAIL mediated apoptosis as evidenced by cell culture and animal model studies. Moreover, we also bring to the limelight radiation induced expression of miRNAs and how miRNAs further control response of cancer cells to radiation.
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