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      Role of circular RNAs and gut microbiome in gastrointestinal cancers and therapeutic targets

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          Abstract

          Gastrointestinal cancers are a huge worldwide health concern, which includes a wide variety of digestive tract cancers. Circular RNAs (circRNAs), a kind of non-coding RNA (ncRNAs), are a family of single-stranded, covalently closed RNAs that have become recognized as crucial gene expression regulators, having an impact on several cellular functions in cancer biology. The gut microbiome, which consists of several different bacteria, actively contributes to the regulation of host immunity, inflammation, and metabolism. CircRNAs and the gut microbiome interact significantly to greatly affect the growth of GI cancer. Several studies focus on the complex functions of circRNAs and the gut microbiota in GI cancers, including esophageal cancer, colorectal cancer, gastric cancer, hepatocellular cancer, and pancreatic cancer. It also emphasizes how changed circRNA expression profiles and gut microbiota affect pathways connected to malignancy as well as how circRNAs affect hallmarks of gastrointestinal cancers. Furthermore, circRNAs and gut microbiota have been recommended as biological markers for therapeutic targets as well as diagnostic and prognostic purposes. Targeting circRNAs and the gut microbiota for the treatment of gastrointestinal cancers is also being continued to study. Despite significant initiatives, the connection between circRNAs and the gut microbiota and the emergence of gastrointestinal cancers remains poorly understood. In this study, we will go over the most recent studies to emphasize the key roles of circRNAs and gut microbiota in gastrointestinal cancer progression and therapeutic options. In order to create effective therapies and plan for the future gastrointestinal therapy, it is important to comprehend the functions and mechanisms of circRNAs and the gut microbiota.

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          NF-κB, inflammation, immunity and cancer: coming of age

          Fourteen years have passed since nuclear factor-κB (NF-κB) was first shown to serve as a molecular lynchpin that links persistent infections and chronic inflammation to increased cancer risk. The young field of inflammation and cancer has now come of age, and inflammation has been recognized by the broad cancer research community as a hallmark and cause of cancer. Here, we discuss how the initial discovery of a role for NF-κB in linking inflammation and cancer led to an improved understanding of tumour-elicited inflammation and its effects on anticancer immunity.
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            Knocking down barriers: advances in siRNA delivery

            Key Points RNA interference (RNAi) is a fundamental pathway in eukaryotic cells by which sequence-specific small interfering RNA (siRNA) is able to silence genes through the destruction of complementary mRNA. RNAi is an important therapeutic tool that can be used to silence aberrant endogenous genes or to knockdown genes essential to the proliferation of infectious organisms. Delivery remains the central challenge to the therapeutic application of RNAi technology. Before siRNA can take effect in the cytoplasm of a target cell, it must be transported through the body to the target site without undergoing clearance or degradation. Currently, the most effective synthetic, non-viral delivery agents of siRNA are lipids, lipid-like materials and polymers. Various cationic agents including stable nucleic acid–lipid particles, lipidoids, cyclodextrin polymers and polyethyleneimine polymers have been used to achieve the successful systemic delivery of siRNA in mammals without inducing significant toxicity. Direct conjugation of delivery agents to siRNA can facilitate delivery. For example, cholesterol-modified siRNA enables targeting to the liver. RNAi therapeutics have progressed to the clinic, where studies are being conducted to determine siRNA efficacy in treating several diseases, including age-related macular degeneration and respiratory syncytial virus. Moving forward, it will be important to pay close attention to the potential nonspecific immunostimulatory effects of siRNA. Modifications to siRNA can be used to minimize stimulation of the immune system, and an increased emphasis must be placed on performing proper controls to ensure that therapeutic effects are sequence-specific.
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              The gut microbiota, bacterial metabolites and colorectal cancer.

              Accumulating evidence suggests that the human intestinal microbiota contributes to the aetiology of colorectal cancer (CRC), not only via the pro-carcinogenic activities of specific pathogens but also via the influence of the wider microbial community, particularly its metabolome. Recent data have shown that the short-chain fatty acids acetate, propionate and butyrate function in the suppression of inflammation and cancer, whereas other microbial metabolites, such as secondary bile acids, promote carcinogenesis. In this Review, we discuss the relationship between diet, microbial metabolism and CRC and argue that the cumulative effects of microbial metabolites should be considered in order to better predict and prevent cancer progression.
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                Author and article information

                Contributors
                Journal
                Noncoding RNA Res
                Noncoding RNA Res
                Non-coding RNA Research
                KeAi Publishing
                2468-0540
                15 December 2023
                March 2024
                15 December 2023
                : 9
                : 1
                : 236-252
                Affiliations
                [a ]Department of Pharmacology and Toxicology, College of Pharmacy, Hawler Medical University, Erbil, Iraq
                [b ]Medical Laboratory Science, College of Health Sciences, Lebanese French University, Kurdistan Region, Erbil, Iraq
                [c ]Department of Biomedical Sciences, College of Science, Cihan University-Erbil, Kurdistan Region, 44001, Iraq
                [d ]Department of Clinical Analysis, College of Pharmacy, Hawler Medical University, Kurdistan Region, Erbil, Iraq
                [e ]Department of Nursing, College of Nursing, Lebanese French University, Kurdistan Region, Erbil, Iraq
                [f ]Department of Pharmaceutical Basic Science, Faculty of Pharmacy, Tishk International University, Erbil, Kurdistan Region, Iraq
                [g ]Institute of Human Genetics, Jena University Hospital, Jena, Germany
                [h ]Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
                Author notes
                []Corresponding author. Institute of Human Genetics, Jena University Hospital, Jena, Germany. Mohammad.Taheri@ 123456uni-jena.de
                [∗∗ ]Corresponding author. Department of Biomedical Sciences, College of Science, Cihan University-Erbil, Kurdistan Region, 44001, Iraq. bashdar.hussen@ 123456hmu.edu.krd
                Article
                S2468-0540(23)00094-X
                10.1016/j.ncrna.2023.12.002
                10771991
                38192436
                75750d4f-dd8b-4c80-af9f-a25445a9e2c8
                © 2023 The Authors

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                : 29 September 2023
                : 10 November 2023
                : 11 December 2023
                Categories
                Article

                circular rnas,gut microbes,gastrointestinal (gi) cancers,therapeutic target

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