Natural products and their putative effect on NORAD
Laura Gebetsberger
2020
unpublished
While the majority of the human genome is transcribed, only a small fraction of these RNA transcripts is ultimately translated into proteins. The plethora of non-coding RNAs have increasingly attracted attention, with the group of long non-coding RNAs (lncRNAs) emerging as particularly interesting, because of their functions in embryonic development, differentiation and disease. Noncoding RNA activated by DNA damage (NORAD) is an abundant and conserved lncRNA that has recently been uncovered as
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... a regulator of genomic stability, mitochondrial function and aging in mammalian cells and tissues. Furthermore, NORAD expression can be increased by cellular stressors, including DNA damage and hypoxia, although the exact involvement of the lncRNA and the functional consequences of its induction in these and other stress response pathways, are not yet understood. Natural products have been investigated for a myriad of human diseases and have emerged as modulators of lncRNAs in several human disease models. Therefore, seven natural products, all known to exhibit anti-cancer, antioxidant, anti-aging and longevity effects among others, were selected to explore a potential effect on NORAD in this thesis. While NORAD +/+ and NORAD -/- cells did not differ in viability or intracellular ROS production upon treatment with the selected compounds, qRT-PCR analysis revealed an induction of NORAD by curcumin at 10 µM, rapamycin at 5 µM and 1 µM and resveratrol at 100 µM. This induction may likely be a result of cellular stress caused by the compounds, as we suggest a possible correlation between an increase in oxidative stress and an increase in NORAD, as well as a potential connection of NORAD induction to p53. These findings therefore emphasize the role of NORAD in cellular stress response and may provide further lines of investigation into the mechanisms and outcomes of NORAD modulation by the hereby tested compounds, as well as the involvement of the lncRNA in other stress response pathways and whether these could be modulated by [...]
doi:10.25365/thesis.64579
fatcat:5gxsf5tyyfgmhikoi62td36uya