Evidence mapPaperPMID 39190492Full record

ArticleJCI insight2024

miR-33 deletion in hepatocytes attenuates MASLD-MASH-HCC progression.

Pablo Fernández-Tussy, Magdalena P Cardelo, Hanming Zhang, Jonathan Sun, Nathan L Price, Nabil E Boutagy, Leigh Goedeke, Martí Cadena-Sandoval, Chrysovalantou E Xirouchaki, Wendy Brown and 7 more

Abstract read
In one paragraph

Article in JCI insight, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Review
  6. Article
  7. Article
  8. Review
  9. Review
  10. Article
  11. Review
  12. Autophagy in the liver.Autophagy reports · 2026
    Review
  13. Article
  14. Review
  15. Therapeutic Applications of Poly-miRNAs and miRNA Sponges.International journal of molecular sciences · 2025
    Review
  16. Review
  17. Review
  18. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors.

Pablo Fernández-TussyVascular Biology and Therapeutics Program.
Magdalena P CardeloVascular Biology and Therapeutics Program.
Hanming ZhangVascular Biology and Therapeutics Program.
Jonathan SunVascular Biology and Therapeutics Program.
Nathan L PriceVascular Biology and Therapeutics Program.
Nabil E BoutagyVascular Biology and Therapeutics Program.
Leigh GoedekeCardiovascular Research Institute and Division of Cardiology, Department of Medicine; and.
Martí Cadena-SandovalDepartment of Pathology & Cell Biology and Naomi Berrie Diabetes Center, Columbia University, New York, New York, USA.
Chrysovalantou E XirouchakiMonash Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.
Wendy BrownDepartment of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia.
Xiaoyong YangDepartment of Comparative Medicine.
Oscar Pastor-RojoVascular Biology and Therapeutics Program.
Rebecca A HaeuslerDepartment of Pathology & Cell Biology and Naomi Berrie Diabetes Center, Columbia University, New York, New York, USA.
Anton M BennettYale Center for Molecular and System Metabolism, and.
Tony TiganisMonash Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia.
Yajaira SuárezVascular Biology and Therapeutics Program.
Carlos Fernández-HernandoVascular Biology and Therapeutics Program.

Funding

Yale Clinical and Translational Science AwardUL1TR001863 · YALE UNIVERSITY · 2025 to 2025
$9.9M
Insights into the molecular mechanisms regulating vascular and immune metabolism in vascular diseasesR35HL155988 · NHLBI · YALE UNIVERSITY · 2022 to 2025
$3.9M
Novel insights into the molecular and cellular mechanism regulating lipid metabolism and atherosclerosisR35HL135820 · NHLBI · YALE UNIVERSITY · PI Carlos Fernandez Hernando · 2022 to 2023
$1.7M
Insulin regulation of hepatic transportR01DK135298 · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2025 to 2025
$668k
NCATS NIH HHS UL1 TR001863NHLBI NIH HHS R00 HL150234NHLBI NIH HHS R35 HL135820NHLBI NIH HHS R35 HL155988NIDDK NIH HHS K01 DK120794NIDDK NIH HHS R01 DK135298
6 · The paper itself

Abstract

The complexity of the mechanisms underlying metabolic dysfunction-associated steatotic liver disease (MASLD) progression remains a significant challenge for the development of effective therapeutics. miRNAs have shown great promise as regulators of biological processes and as therapeutic targets for complex diseases. Here, we study the role of hepatic miR-33, an important regulator of lipid metabolism, during the progression of MASLD and the development of hepatocellular carcinoma (HCC). We report that miR-33 was elevated in the livers of humans and mice with MASLD and that its deletion in hepatocytes (miR-33 HKO) improved multiple aspects of the disease, including steatosis and inflammation, limiting the progression to metabolic dysfunction-associated steatotic hepatitis (MASH), fibrosis, and HCC. Mechanistically, hepatic miR-33 deletion reduced lipid synthesis and promoted mitochondrial fatty acid oxidation, reducing lipid burden. Additionally, absence of miR-33 altered the expression of several known miR-33 target genes involved in metabolism and resulted in improved mitochondrial function and reduced oxidative stress. The reduction in lipid accumulation and liver injury resulted in decreased YAP/TAZ pathway activation, which may be involved in the reduced HCC progression in HKO livers. Together, these results suggest suppressing hepatic miR-33 may be an effective therapeutic approach to temper the development of MASLD, MASH, and HCC in obesity.

Indexed as

Carcinoma, HepatocellularDisease ProgressionHepatocytesLiver NeoplasmsMicroRNAsAnimalsDisease Models, AnimalFatty LiverHumansLipid MetabolismLiverMaleMiceMice, KnockoutMicroRNAsMIRN33a microRNA, humanMirn33 microRNA, mouseFatty acid oxidationHepatologyLiver cancerMetabolismNoncoding RNAs

Identifiers

PMID39190492
PMCPMC11466198

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.