Linc01271 promotes lipid synthesis and MASLD/MASH progression via miR-149-3p/RAB35 axis

Area of Science:

• Hepatology
• Molecular Biology
• Genetics

Background:

• Metabolic associated steatohepatitis (MASH) is a severe liver condition linked to metabolic dysfunction.
• The precise molecular drivers of MASH progression are not fully understood.
• Identifying novel molecular targets is crucial for developing effective MASH therapies.

Purpose of the Study:

• To investigate the role of long non-coding RNA Linc01271 in the pathogenesis of MASH.
• To elucidate the molecular mechanisms involving the miR-149-3p/RAB35 axis and PI3K/AKT/mTOR pathway in MASH.
• To assess Linc01271 as a potential therapeutic target for MASH.

Main Methods:

• Transcriptome sequencing and RT-qPCR to analyze Linc01271 expression in MASH tissues.
• In vitro experiments using THLE-2 cells to assess the effects of Linc01271 knockdown or overexpression on lipid metabolism and inflammation.
• Dual-luciferase reporter assays to confirm interactions between Linc01271 and miR-149-3p.
• In vivo studies in mice to evaluate the impact of Linc01271 knockdown on MASH progression.

Main Results:

• Linc01271 was significantly upregulated in MASH tissues, correlating with increased lipid accumulation and inflammation.
• Linc01271 knockdown in cells reduced lipid synthesis and pro-inflammatory cytokine expression.
• Linc01271 was confirmed to interact with miR-149-3p, influencing the regulation of RAB35.
• Linc01271 knockdown in mice ameliorated MASH, reducing liver injury and metabolic dysfunction markers.

Conclusions:

• Linc01271 promotes MASH by enhancing lipid synthesis and inflammatory responses via the miR-149-3p/RAB35 axis and PI3K/AKT/mTOR pathway.
• Linc01271 represents a promising therapeutic target for MASLD/MASH.
• Further investigation is needed to develop Linc01271-targeted therapies for clinical application.