Connection between Radiation-Regulating Functions of Natural Products and miRNAs Targeting Radiomodulation and Exosome Biogenesis

Abstract

Exosomes are cell-derived membranous structures primarily involved in the delivery of the payload to the recipient cells, and they play central roles in carcinogenesis and metastasis. Radiotherapy is a common cancer treatment that occasionally generates exosomal miRNA-associated modulation to regulate the therapeutic anticancer function and side effects. Combining radiotherapy and natural products may modulate the radioprotective and radiosensitizing responses of non-cancer and cancer cells, but there is a knowledge gap regarding the connection of this combined treatment with exosomal miRNAs and their downstream targets for radiation and exosome biogenesis. This review focuses on radioprotective natural products in terms of their impacts on exosomal miRNAs to target radiation-modulating and exosome biogenesis (secretion and assembly) genes. Several natural products have individually demonstrated radioprotective and miRNA-modulating effects. However, the impact of natural-product-modulated miRNAs on radiation response and exosome biogenesis remains unclear. In this review, by searching through PubMed/Google Scholar, available reports on potential functions that show radioprotection for non-cancer tissues and radiosensitization for cancer among these natural-product-modulated miRNAs were assessed. Next, by accessing the miRNA database (miRDB), the predicted targets of the radiation- and exosome biogenesis-modulating genes from the Gene Ontology database (MGI) were retrieved bioinformatically based on these miRNAs. Moreover, the target-centric analysis showed that several natural products share the same miRNAs and targets to regulate radiation response and exosome biogenesis. As a result, the miRNA–radiomodulation (radioprotection and radiosensitization)–exosome biogenesis axis in regard to natural-product-mediated radiotherapeutic effects is well organized. This review focuses on natural products and their regulating effects on miRNAs to assess the potential impacts of radiomodulation and exosome biogenesis for both the radiosensitization of cancer cells and the radioprotection of non-cancer cells.

Nrf-2 as a novel target in radiation induced lung injury

“…At present, plant antioxidants have gradually gained attention in the prevention and treatment of RILI due to their advantages of comprehensive source, low side effects, and high patient acceptance, and have potential effects on radiosensitization of cancer cells and radiation protection of non-cancer cells [ 150 ]. Polyphenols in the diet, such as curcumin, resveratrol, and myrtol, can regulate the activation of Nrf-2 and biosynthesis of glutathione to remove ROS, thereby regulating inflammatory factors in macrophages and lung epithelial cells to play a therapeutic role [ 7 , 151 , 152 ].…”

Exosomes and exosomal miRNAs: A new avenue for the future treatment of rheumatoid arthritis

“…To date, 2838 kinds of miRNAs have been found in exosome bodies, and the expression levels of these exosome miRNAs differ according to disease and physiological conditions [ 131 , 132 ]. The types of exosomal miRNAs mainly include cell-derived miRNAs, which originate from cells and are released into the extracellular environment through the secretion of exosomes [ 133 ]. These cell-derived miRNAs may be involved in the cellular regulation of gene expression; environment-responsive miRNAs; the release of several exosome miRNAs is regulated by environmental stimuli, and these miRNAs may play important roles in responding to environmental stress; signaling-regulatory miRNAs and exosome miRNAs are considered to be molecules that can transmit signals between cells and can influence the gene expression and function of target cells; and disease-associated miRNAs and some exosome miRNAs are associated with the occurrence and development of diseases; therefore, they are studied as potential biomarkers or therapeutic targets [ 134 ].…”

Mechanistic role of pyroptosis in tumor microenvironment and tumor immunotherapy

“…Evolution of the non-coding RNA concept from 'junk' transcriptional products to functional regulatory molecules that mediate cellular processes has opened new horizons for the identification of different mechanisms. Discovery and characterization of microRNAs (miRNAs) (29)(30)(31)(32)(33)(34)(35)(36), long non-coding RNAs (lncRNAs) (37)(38)(39)(40)(41) and circular RNAs have revealed the diversity of their regulatory roles.…”