Profiling of extracellular vesicle‐bound miRNA to identify candidate biomarkers of chronic alcohol drinking in nonhuman primates

• Published in: Alcoholism, clinical and experimental research clinical and experimental research, 2022-02, Vol.46 (2), p.221-231
• Main Authors: Lewis, Sloan A., Doratt, Brianna, Sureshchandra, Suhas, Pan, Tianyu, Gonzales, Steven W., Shen, Weining, Grant, Kathleen A., Messaoudi, Ilhem
• Format: Article
• Language: English
• Subjects: Alcohol; Alcohol Drinking - blood; Alcohol use; Alcoholism; Animals; Biomarkers; Biomarkers - blood; Dose-Response Relationship, Drug; Down-Regulation; Drinking behavior; Ethanol; Ethanol - administration & dosage; Ethanol - blood; Extracellular vesicles; Extracellular Vesicles - drug effects; Female; Humans; Inflammation; Leukocytes (mononuclear); Liver cancer; Liver diseases; Macaca mulatta; Male; MicroRNAs; MicroRNAs - blood; miRNA; nonhuman primates; Peripheral blood mononuclear cells; Tumor necrosis factor-α
• ISSN: 0145-6008; 1530-0277
• DOI: 10.1111/acer.14760

Background Long‐term alcohol drinking is associated with numerous health complications including susceptibility to infection, cancer, and organ damage. However, due to the complex nature of human drinking behavior, it has been challenging to identify reliable biomarkers of alcohol drinking behavior prior to signs of overt organ damage. Recently, extracellular vesicle‐bound microRNAs (EV‐miRNAs) have been found to be consistent biomarkers of conditions that include cancer and liver disease. Methods In this study, we profiled the plasma EV‐miRNA content by miRNA‐Seq from 80 nonhuman primates after 12 months of voluntary alcohol drinking. Results We identified a list of up‐ and downregulated EV‐miRNA candidate biomarkers of heavy drinking and those positively correlated with ethanol dose. We overexpressed these candidate miRNAs in control primary peripheral immune cells to assess their potential functional mechanisms. We found that overexpression of miR‐155, miR‐154, miR‐34c, miR‐450a, and miR‐204 led to increased production of the inflammatory cytokines TNFα or IL‐6 in peripheral blood mononuclear cells after stimulation. Conclusion This exploratory study identified several EV‐miRNAs that could serve as biomarkers of long‐term alcohol drinking and provide a mechanism to explain alcohol‐induced peripheral inflammation. Due to the complex nature of human drinking behavior, it has been challenging to identify reliable biomarkers of alcohol use that could be used to determine drinking behavior prior to signs of overt organ damage. This study profiles the plasma EV‐miRNA content of 80 non‐human primates after 12 months of voluntary ethanol drinking by miRNA‐Seq. We identified several EV‐miRNA that could serve as biomarkers of long‐term alcohol drinking as well as provided a mechanism for alcohol‐induced peripheral inflammation.