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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Inflammation
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1518807
This article is part of the Research Topic Molecular Mechanisms and Therapeutic Strategies in Inflammation View all 12 articles

Linc01271 Promotes Lipid Synthesis and MASH progression via miR-149-3p/RAB35 Axis

Provisionally accepted
Xiangyu Zhai Xiangyu Zhai 1Xinlu Zhang Xinlu Zhang 2Yanmei Wu Yanmei Wu 3Hao Zhang Hao Zhang 4Huaxin Zhou Huaxin Zhou 1Zili Zhang Zili Zhang 5Bin Jin Bin Jin 1,4*
  • 1 The Second Hospital of Shandong University, Jinan, Shandong Province, China
  • 2 Jinan Central Hospital, Jinan, Shandong Province, China
  • 3 Shandong Maternal and Child Health Hospital, Jinan, Shandong Province, China
  • 4 Qilu Hospital, Shandong University, Jinan, China
  • 5 Fourth People’s Hospital of Jinan, Jinan, Shandong Province, China

The final, formatted version of the article will be published soon.

    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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