Journal
JOURNAL OF MOLECULAR ENDOCRINOLOGY
Volume 68, Issue 1, Pages 35-49Publisher
BIOSCIENTIFICA LTD
DOI: 10.1530/JME-20-0324
Keywords
miR-23a/b-3p; triglyceride accumulation; 5 '-UTR; Srebp-1c; Fas
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Funding
- National Key R&D Program of China [2018YFC2000100]
- National Natural Science Foundation of China [81770858, 81770228, 81600618, 81470427]
- Beijing Natural Science Foundation [7182144]
- Beijing Hospital Nova Project [BJ-2018-138]
- Non-profit Central Research Institute Fund of the Chinese Academy of Medical Sciences [2018RC310025]
- Peking Union Medical College Graduate Innovation Fund Project [2018-0710-05]
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miR-23a/b-3p enhances the stability of Srebp-1c and Fas mRNA by binding to their 5'-UTR, promoting triglyceride accumulation in hepatocytes.
miR-23a-3p and miR-23b-3p are members of the miR-23 similar to 27 similar to 24 similar to 2 superfamily. The role of miR-23a/b-3p in regulating hepatic lipid accumulation is still unknown. Here, we found that increased miR-23a-3p and miR-23b-3p levels were accompanied by an increase in the protein levels of the sterol regulatory element-binding protein-1 (SREBP-1) and fatty acid synthase (FAS) in the steatotic livers of mice fed a high-fat diet and leptin receptor-deficient type 2 diabetic mice (db/db). Importantly, overexpression of miR-23a/b-3p in Hep1-6 cells elevated the intracellular triglyceride level and upregulated the expression of Srebp-1c and Fas. Taken together, these results suggested that miR-23a/b-3p enhanced mRNA stability by binding the 5'-UTR of Srebp-1c and Fas mRNA, thereby promoting triglyceride accumulation in hepatocytes.
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