Disease-Associated Regulation of Non-Coding RNAs by Resveratrol: Molecular Insights and Therapeutic Applications

Abstract

There have been significant advances, particularly over the last 20 years, in the identification of non-coding RNAs (ncRNAs) and their pathophysiological role in a wide range of disease states, particularly cancer and other chronic conditions characterized by excess inflammation and oxidative stress such as atherosclerosis, diabetes, obesity, multiple sclerosis, osteoporosis, liver and lung fibrosis. Such discoveries have potential therapeutic implications as a better understanding of the molecular mechanisms underpinning the effects of ncRNAs on critical homeostatic control mechanisms and biochemical pathways might lead to the identification of novel druggable targets. In this context, increasing evidence suggests that several natural compounds can target ncRNAs at different levels and, consequently, influence processes involved in the onset and progression of disease states. The natural phenol resveratrol has been extensively studied for therapeutic purposes in view of its established anti-inflammatory and antioxidant effects, particularly in disease states such as cancer and cardiovascular disease that are associated with human aging. However, increasing in vitro and in vivo evidence also suggests that resveratrol can directly target various ncRNAs and that this mediates, at least in part, its potential therapeutic effects. This review critically appraises the available evidence regarding the resveratrol-mediated modulation of different ncRNAs in a wide range of disease states characterized by a pro-inflammatory state and oxidative stress, the potential therapeutic applications, and future research directions.

Disease-associated regulation of gene expression by resveratrol: Special focus on the PI3K/AKT signaling pathway

“…Notably, resveratrol has been found to affect the expression of several genes including cytokine coding genes, caspases, matrix metalloproteinases, adhesion molecules, and growth factors [ 101 ]. In addition to the mentioned protein coding genes, evidence from in vitro and in vivo assays has shown the direct effects of resveratrol on several non-coding genes and possible implication of these transcripts in the therapeutic effects of resveratrol [ 107 ]. Moreover, it can modulate the activity of several signaling pathways such as PI3K/AKT, Wnt, NF-κB, and Notch pathways [ 101 ].…”

An overview of natural products that modulate the expression of non-coding RNAs involved in oxidative stress and inflammation-associated disorders

“…Resveratrol is a polyphenolic phytoalexin derived from many plants such as grapes; groundnut, pine, and vine which revealed anti-cancer effects ( Rauf et al, 2018 ). There have been several research demonstrating the regulation of ncRNAs by resveratrol ( Giordo et al, 2022 ). It inhibits breast cancer cell proliferation by inducing the expression of tumor suppressor miRNAs (miR-34a, miR-424, and miR-503) through the p53 pathway ( Otsuka et al, 2018 ) and lncRNA LINC00978 ( Deng et al, 2016 ).…”

“…Yan et al (2015), AlAameri et al (2017),Beaver et al (2017),, Palmieri et al (2017,Saghafi et al (2019),Chen et al (2021a),Chen et al (2021b),Irshad and Husain (2021),Kalhori et al (2021),Ma et al (2021),Mishra et al (2021),Ruiz-Manriquez et al (2021),Cesmeli et al (2022),Giordo et al (2022), lncRNA sONE, MALAT 1 Bladé et al (2013), Mishra et al (2019), Ren et al (2020), Ramanujam et al (2021), Elham et al…”

Modulation of the ubiquitin‐proteasome system by phytochemicals: Therapeutic implications in malignancies with an emphasis on brain tumors

“…19,[291][292][293][294] It is appropriate to consider polyphenols, such as those found in green tea and red grapes, as future therapeutics due to their broad range of biological functions, such as antioxidant, free radical scavenging, anti-inflammatory, and metal chelating effects. [295][296][297][298][299][300][301][302] Natural flavonoids have been demonstrated in recent studies to alter the action of the proteasome, a multi-enzyme, multi-catalytic complex found in the cytoplasm and nucleus of all eukaryotic cells. The proteasome controls various biological processes, including cell cycle regulation, apoptosis, and the degradation of oxidative, unfolded, and misfolded proteins, as well as antigen presentation.…”

“…Modern nutritional investigations have demonstrated the beneficial effects of polyphenolic antioxidants, found in fruits, vegetables, and their juices, in preventing and treating a broad variety of diseases, including cancer 19,291–294 . It is appropriate to consider polyphenols, such as those found in green tea and red grapes, as future therapeutics due to their broad range of biological functions, such as antioxidant, free radical scavenging, anti‐inflammatory, and metal chelating effects 295–302 . Natural flavonoids have been demonstrated in recent studies to alter the action of the proteasome, a multi‐enzyme, multi‐catalytic complex found in the cytoplasm and nucleus of all eukaryotic cells.…”