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project","award":["2021-YF05-00800-SN"],"award-info":[{"award-number":["2021-YF05-00800-SN"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Ectopic fat deposition in the liver, known as non-alcoholic fatty liver disease (NAFLD), affects up to 30% of the worldwide population. miRNA-122, the most abundant liver-specific miRNA, protects hepatic steatosis and inhibits cholesterol and fatty acid synthesis in NAFLD. Previously, we have shown that compared with its expression in healthy controls, miRNA-122 decreased in the liver tissue but gradually increased in the serum of patients with non-alcoholic fatty liver disease and non-alcoholic steatohepatitis, suggesting that miRNA-122 could have been transported to the serum. Here, we aimed to confirm and unravel the mechanism of transportation of miRNA-122 to extra-hepatocytes. Our findings showed a decrease in the intra-hepatocyte miRNA-122 and an increase in the extra-hepatocyte (medium level) miRNA-122, suggesting the miRNA-122 \u201cescaped\u201d from the intra-hepatocyte due to an increased extra-hepatocyte excretion. Using bioinformatics tools, we showed that miRNA-122 binds to circPI4KB, which was further validated by an RNA pull-down and luciferase reporter assay. The levels of circPI4KB in intra- and extra-hepatocytes corresponded to that of miRNA-122, and the overexpression of circPI4KB increased the miRNA-122 in extra-hepatocytes, consequently accomplishing a decreased protective role of miRNA-122 in inhibiting the lipid deposition. The present study provides a new explanation for the pathogenesis of the hepatic lipid deposition in NAFLD.<\/jats:p>","DOI":"10.3390\/ijms24021297","type":"journal-article","created":{"date-parts":[[2023,1,9]],"date-time":"2023-01-09T06:38:27Z","timestamp":1673246307000},"page":"1297","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["CircRNA-PI4KB Induces Hepatic Lipid Deposition in Non-Alcoholic Fatty Liver Disease by Transporting miRNA-122 to Extra-Hepatocytes"],"prefix":"10.3390","volume":"24","author":[{"given":"Chang-Hai","family":"Liu","sequence":"first","affiliation":[{"name":"Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu 610041, China"},{"name":"Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Disease, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Jiang","sequence":"additional","affiliation":[{"name":"Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu 610041, China"},{"name":"Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Disease, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingmin","family":"Zeng","sequence":"additional","affiliation":[{"name":"Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu 610041, China"},{"name":"Division of Infectious Diseases, State Key Laboratory of Biotherapy and Center of Infectious Disease, West China Hospital, Sichuan University, Chengdu 610041, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongbo","family":"Wu","sequence":"additional","affiliation":[{"name":"Center of Infectious Diseases, West China 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1053\/j.gastro.2020.11.051","article-title":"Aga clinical practice update on lifestyle modification using diet and exercise to achieve weight loss in the management of nonalcoholic fatty liver disease: Expert review","volume":"160","author":"Younossi","year":"2021","journal-title":"Gastroenterology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"m4747","DOI":"10.1136\/bmj.m4747","article-title":"Management of non-alcoholic fatty liver disease","volume":"372","author":"Petroni","year":"2021","journal-title":"BMJ"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1001\/jama.2020.2298","article-title":"Nonalcoholic steatohepatitis: A 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