The genome integrity plays a critical role in the maintaining of organism functioning and determines the rate of aging. This is ensured by the efficient work of mechanisms of DNA damage response, and their regulation by small non-coding RNAs - microRNAs. At the same time, several bioactive substances can modulate microRNAs expression and stimulate cellular defence systems. Present to you the article which describes the influence of bioactive compounds on the DDR-MicroRNA system in the context of aging and carcinogenesis.
Authors: Felicia Carotenuto, Maria C. Albertini, Dario Coletti, Alessandra Vilmercati, Luigi Campanella, Zbigniew Darzynkiewicz, and Laura Teodori
Abstract
The DNA damage response (DDR) is a molecular mechanism that cells have evolved to sense DNA damage (DD) to promote DNA repair, or to lead to apoptosis, or cellular senescence if the damage is too extensive. Recent evidence indicates that microRNAs (miRs) play a critical role in the regulation of DDR. Dietary bioactive compounds through miRs may affect activity of numerous genes. Among the most studied bioactive compounds modulating expression of miRs are epi-gallocatechin-3-gallate, curcumin, resveratrol and n3-polyunsaturated fatty acids. To compare the impact of these dietary compounds on DD/DDR network modulation, we performed a literature search and an in silico analysis by the DIANA-mirPathv3 software. The in silico analysis allowed us to identify pathways shared by different miRs involved in DD/DDR vis-à-vis the specific compounds. The results demonstrate that certain miRs (e.g., -146, -21) play a central role in the interplay among DD/DDR and the bioactive compounds. Furthermore, some specific pathways, such as "fatty acids biosynthesis/metabolism", "extracellular matrix-receptor interaction" and "signaling regulating the pluripotency of stem cells", appear to be targeted by most miRs affected by the studied compounds. Since DD/DDR and these pathways are strongly related to aging and carcinogenesis, the present in silico results of our study suggest that monitoring the induction of specific miRs may provide the means to assess the antiaging and chemopreventive properties of particular dietary compounds.
