Noncoding RNA and Alcohol Use Disorder: A Scoping Review of Current Research and Knowledge Gaps.

Background: Alcohol use and misuse can result in substantial disease burden and mortality, with significant public health and social costs. The need for better diagnoses and medications development for all conditions associated with alcohol use emphasizes the need for research into underlying molecular mechanisms. Noncoding ribonucleic acids (ncRNAs) are an explanatory mechanism for transducing environmental effects into cells and tissues. ncRNAs are regulatory RNAs that are diverse in size and function and greatly outnumber protein-coding RNAs in mammals. ncRNAs may play a major role in the pathogenesis and consequences of alcohol use and misuse, and studies in this area could pave the way to developing novel methods of diagnosis and therapy.

Objectives: This scoping review examines the extent, range, and nature of the research linking ncRNAs to alcohol, with a focus on identifying gaps in the existing literature.

Eligibility criteria: This scoping review followed the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews." Peer-reviewed journal articles for all species, including human, animal, or cells, published until December 2023, were included.

Sources of evidence: Publications were retrieved using keyword searches in three online databases: Medline (Ovid), Embase (Ovid), and Academic Search Ultimate (EBSCO).

Chart methods: Identified articles were imported in Covidence systematic review software for screening. Each article was evaluated by at least two independent reviewers, and only those receiving votes from both were included in the review. Key findings were then extracted from the included studies, further analyzed, and summarized in a table and figures using Microsoft Excel. Details, including year of publication, species, sex, sample type, and sample processing methods for different types of ncRNAs (i.e., microRNAs [miRNAs], long noncoding RNAs [lncRNAs], circular RNAs [circRNAs]) were also reported.

Results: In total, 3,358 studies were identified and imported in Covidence. After removal of duplicates, 1,937 studies were processed for title and abstract screening, and 400 studies were subsequently selected for full-text screening. From these, 338 studies were included in the scoping review. In total, 3,020 initially captured studies were excluded. Among all ncRNAs, miRNAs were the most frequently investigated, followed by lncRNAs and circRNAs. Whereas many studies investigated ncRNA associations with alcohol phenotypes, mechanistic studies were more limited. Studies spanned pathologies related to alcohol use across tissues and organs, including liver, brain, heart, pancreas, placenta, gastrointestinal system, muscle, and bone. However, key variables, including biological sex, age, and genetic variation, were not adequately addressed. The analyses uncovered significant gaps in the research literature, relating primarily to underlying mechanisms.

Conclusions: The field of ncRNA research in pathologies associated with alcohol use is still emerging. Given the enormous sizes and species variations of mammalian ncRNA genomes, a significant amount of research is needed to identify relevant ncRNAs in different organs, and at all stages of pathology, and to identify underlying mechanisms. Initial studies show promise that ncRNA research could significantly improve the diagnosis and treatment of alcohol use disorder.