Evidence for a radiation-responsive ‘p53 gateway’ contributing significantly to the radioresistance of lepidopteran insect cells

Abstract

Recently, we have demonstrated that microRNA-31 (miR-31) overexpression is inherent to radiation-induced cell death in the highly radioresistant Sf9 insect cells, and regulates pro-apoptotic Bax translocation to mitochondria. In the present study, we report that at sub-lethal radiation doses for Sf9 cells, miR-31 is significantly downregulated and is tightly regulated by an unusual mechanism involving p53. While ectopic overexpression of a well-conserved Sfp53 caused typical apoptosis, radiation-induced p53 accumulation observed selectively at sub-lethal doses failed to induce cell death. Further investigation of this paradoxical response revealed an intriguing phenomenon that sub-lethal radiation doses result in accumulation of a ‘hyper-phosphorylated’ Sfp53, which in turn binds to miR-31 genomic location and suppresses its expression to prevent cell death. Interestingly, priming cells with sub-lethal doses even prevented the apoptosis induced by lethal radiation or ectopic Sfp53 overexpression. On the other hand, silencing p53 increased radiation-induced cell death by inhibiting miR-31 downregulation. This study thus shows the existence of a unique radiation-responsive ‘p53 gateway’ preventing miR-31-mediated apoptosis in Sf9 cells. Since Sfp53 has a good functional homology with human p53, this study may have significant implications for effectively modulating the mammalian cell radioresistance.

The role of microRNAs and nanoparticles in ovarian cancer: a review

“…For example, p53-mediated upregulation of miR-34 is known to induce cell death in C. elegans as well as in mammalian cells. Many other miRNAs other than miR-34 family members are now known to be regulated by p53, viz., miR-194, miR-207, miR-107, miR-215, miR-192, miR-16-1, miR-143, miR-145 and miR-216 [35]. It has been shown that p53 transcriptionally induces miR-34 expression, and this induction is important in p53-mediated apoptosis of cancer cells [36,37].…”

Clinical impact of melatonin on breast cancer patients undergoing chemotherapy; effects on cognition, sleep and depressive symptoms: A randomized, double-blind, placebo-controlled trial

“…The neurotoxicity associated with chemotherapy for breast cancer is also substantiated by the persistent cognitive deficits related to volume reduction in the hippocampal gray matter one year after treatment completion [7]. Also, there is evidence that the reduction in hippocampal volume is associated with a decrease in cognitive function in patients with major depression [8]. The mechanisms underpinning these symptoms need to be further investigated.…”

Application of Nanomaterials in Biomedical Imaging and Cancer Therapy

“…The contrast agents have long blood half-life (40 h) that provides better tumour uptake and clearance from the liver when compared to Au NPs. The agents also efficiently accumulate in tumours and provide high contrast vascular tumour imaging [ 44 ]. In the imaging of thyroid diseases and radionuclide therapy, iodine has been routinely used due to its high affinity for thyroid and relatively long half-life (8.01 days).…”