ORIGINAL RESEARCH article
Front. Immunol.
Sec. Inflammation
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1518807
This article is part of the Research TopicMolecular Mechanisms and Therapeutic Strategies in InflammationView all 15 articles
Linc01271 Promotes Lipid Synthesis and MASH progression via miR-149-3p/RAB35 Axis
Provisionally accepted
- 1The Second Hospital of Shandong University, Jinan, Shandong Province, China
- 2Jinan Central Hospital, Jinan, Shandong Province, China
- 3Shandong Maternal and Child Health Hospital, Jinan, Shandong Province, China
- 4Qilu Hospital, Shandong University, Jinan, China
- 5Fourth People’s Hospital of Jinan, Jinan, Shandong Province, China
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Metabolic associated steatohepatitis (MASH) is a severe form of metabolic dysfunctionassociated steatotic liver disease (MASLD) characterized by hepatocellular injury, inflammation, and fibrosis. Despite advances in understanding its pathophysiology, the molecular mechanisms driving MASH progression remain unclear. This study investigates the role of long non-coding RNA Linc01271 in MASH pathogenesis, ant its involvement in the miR-149-3p/RAB35 axis and PI3K/AKT/mTOR signaling pathway.Transcriptome sequencing and RT-qPCR revealed significant upregulation of Linc01271 in MASH tissues, which correlated with lipid accumulation and inflammatory responses.Knockdown of Linc01271 in THLE-2 cells reduced lipid droplet formation, triglyceride and cholesterol levels, and the expression of lipid metabolism-related genes (CD36, ACC1, FASN) and pro-inflammatory cytokines (IL-6, IL-8, TGF-β1). Conversely, Linc01271 overexpression had the opposite effect. Dual-luciferase reporter assays confirmed Linc01271's interaction with miR-149-3p, which regulates RAB35, a downstream target of miR-149-3p. Knockdown of Linc01271 in mice attenuated MASH progression, reducing body weight, liver weight, blood glucose levels, and liver injury markers. These findings demonstrate that Linc01271 promotes lipid synthesis and inflammatory responses through the miR-149-3p/RAB35 axis and PI3K/AKT/mTOR pathway, highlighting its potential as a therapeutic target for MASH. Further research is warranted to develop therapeutic agents targeting Linc01271 for clinical applications.
Keywords: MASH, MASLD, LINC01271, Lipid Metabolism, miR-149-3p, Rab35
Received: 29 Oct 2024; Accepted: 20 Jan 2025.
Copyright: © 2025 Zhai, Zhang, Wu, Zhang, Zhou, Zhang and Jin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Bin Jin, Qilu Hospital, Shandong University, Jinan, China
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