miR-23a/b-3p promotes hepatic lipid accumulation by regulating Srebp-1c and Fas

in Journal of Molecular Endocrinology
Authors:
Linfang Li Graduate School of Peking Union Medical College, Beijing, China
The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Beijing Hospital, National Center of Gerontology, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China

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Xiaoyi Zhang The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Beijing Hospital, National Center of Gerontology, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China

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Hangjiang Ren Graduate School of Peking Union Medical College, Beijing, China

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Xiuqing Huang The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Beijing Hospital, National Center of Gerontology, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China

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Tao Shen The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Beijing Hospital, National Center of Gerontology, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China

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Weiqing Tang The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Beijing Hospital, National Center of Gerontology, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China

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Lin Dou The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Beijing Hospital, National Center of Gerontology, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China

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https://orcid.org/0000-0002-4635-618X
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Jian Li Graduate School of Peking Union Medical College, Beijing, China
The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Beijing Hospital, National Center of Gerontology, National Health Commission, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China

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Correspondence should be addressed to L Dou or J Li: doulin4623@bjhmoh.cn or lijian@bjhmoh.cn
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miR-23a-3p and miR-23b-3p are members of the miR-23~27~24-2 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.

Supplementary Materials

    • Supplemental Figure 1 The whole blot bind of SREBP-1. (A)The whole blot of SREBP-1 in Hep1-6 cell. There were two predominant bands (an active cleaved band at ~68 kDa and an inactive precursor band at ~120 kDa) (B) The original band of Fig 4C, and we showed active cleaved band of SREBP1 at ~68 kDa.
    • Supplemental Figure 2 The mutation site of Srebp-1c and Fas. (A)The mutation site of Srebp-1c that binds with miR-23a-3p. (B) The mutation site of Srebp-1c that binds with miR-23b-3p.(C) The mutation site of Fas that binds with miR-23a-3p.(D) The mutation site of Fas that binds with miR-23b-3p.

 

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