miR-134-3p Deficiency-Induced Methionine Metabolism Promotes Fibrosis via SLC25A33 in OSF

Area of Science:

• Molecular Biology
• Cell Biology
• Biochemistry

Background:

• Fibrosis involves excessive collagen deposition by fibroblasts, impacting organ function.
• Fibroblast phenotype is regulated by metabolic reprogramming, with microRNAs playing a role in fibrosis.
• Oral submucous fibrosis (OSF) pathogenesis involves fibroblast dysfunction and metabolic alterations.

Purpose of the Study:

• Identify microRNAs (miRNAs) involved in oral submucous fibrosis (OSF) pathogenesis.
• Investigate the role of a specific miRNA in fibroblast phenotypic transformation in OSF.
• Explore the molecular mechanisms linking miRNA, metabolism, and collagen synthesis in OSF.

Main Methods:

• RNA sequencing (RNA-seq) for differential miRNA expression analysis in OSF tissues.
• Quantitative real-time PCR (qPCR) to assess collagen synthesis and miRNA levels.
• Bioinformatic analysis, immunoblotting, ELISA, and luciferase reporter assays to elucidate molecular pathways and targets.

Main Results:

• Hsa-miR-134-3p was found to be underexpressed in fibrotic tissues and saliva of OSF patients.
• Arecoline exposure reduced hsa-miR-134-3p levels, increasing collagen synthesis.
• Hsa-miR-134-3p was identified to directly target SLC25A33, regulating methionine metabolism via the mTOR pathway.

Conclusions:

• MiR-134-3p underexpression in fibroblasts contributes to OSF pathogenesis.
• The miR-134-3p/SLC25A33 axis regulates methionine metabolism and collagen synthesis through the mTOR pathway.
• Targeting the miR-134-3p pathway may offer a therapeutic strategy for OSF.