RP13-516M14.1 Regulates Autophagy Through miR-429 via Both a ceRNA Network and Direct Interaction.

Osteoarthritis (OA), characterized by progressive cartilage degradation, is a leading cause of chronic disability in older adults. Although the molecular mechanisms underlying OA remain incompletely understood, emerging evidence suggests that long non-coding RNAs (lncRNAs) play critical regulatory roles. Recently, we identified a previously uncharacterized lncRNA, RP13-516M14.1, that regulates autophagy in OA chondrocytes. In this study, we aimed to elucidate the mechanism of RP13-516M14.1 in OA pathogenesis. The expression of RP13-516M14.1 was assessed in OA cartilage samples. Its biological functions were investigated using RNA sequencing, RT-qPCR, western blotting, LC3 puncta imaging, transmission electron microscopy (TEM), and atomic force microscopy (AFM) nanoindentation. Its interactions with miR-429 were verified by RNA pull-down assays, RNA immunoprecipitation, fluorescence in situ hybridization (FISH), and dual-luciferase reporter assays. RP13-516M14.1 was identified as key regulator of autophagy, maintaining cartilage homeostasis through modulation of miR-429. Knockdown of RP13-516M14.1 exacerbated OA phenotypes both in vitro and in vivo, while its overexpression protected cartilage by promoting autophagy via miR-429/DDIT4 axis. Notebly, RP13-516M14.1 functioned both as a competitive endogenous RNA (ceRNA) sponging miR-429 and directly regulating its expression. Our study highlights the critical role of RP13-516M14.1 in regulating autophagy in chondrocytes and suggests its potential as a therapeutic target for OA treatment.