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

Fibrosis is a disease characterized by excessive collagen deposition by fibroblasts, leading to tissue and organ dysfunction. Fibroblasts are the primary effector cells, and their functional phenotype is regulated by various factors, with metabolic reprogramming being a crucial one. Previous studies have shown that microRNAs induce hypoxia, abnormal energy metabolism, and promote fibrosis. Our research aimed to identify the miRNA associated with oral submucous fibrosis (OSF) pathogenesis and to preliminarily explore its role in the phenotypic transformation of fibroblasts.

RNA-seq was used to analyze the differential expression of miRNA in OSF and normal tissues, followed by validation in clinical samples (n = 14), saliva (n = 65), and animal models (n = 16). The effect of hsa-miR-134-3p on collagen synthesis was detected by qPCR. Bioinformatic, immunoblot, and Elisa methods were used to analyze the correlation between hsa-miR-134-3p and methionine metabolism, as well as the mTOR pathway. Finally, the luciferase reporter gene assay was used to identify the target gene of hsa-miR-134-3p.

Hsa-miR-134-3p is underexpressed in fibrotic tissues. Arecoline can promote collagen synthesis by reducing hsa-miR-134-3p. Bioinformatic analysis indicated that hsa-miR-134-3p is associated with methionine metabolism and mTOR signaling, and immunoblot and ELISA methods revealed that hsa-miR-134-3p regulates methionine metabolism via the mTOR pathway. Ultimately, hsa-miR-134-3p was identified to directly target SLC25A33 in fibroblasts using the luciferase reporter gene assay.

In summary, the findings suggested that miR-134-3p is underexpressed in fibroblasts, which directly binds to SLC25A33, leading to degradation of SLC25A33 mRNAs. SLC25A33 induces methionine metabolism reprogramming to promote collagen synthesis through the mTOR pathway in OSF.