RNA-seq analysis of human healthy and osteoarthritis meniscus reveals autophagy-related mRNAs and long noncoding RNAs

Aim To identify transcript level differences between healthy and osteoarthritis meniscus in human keen joint using RNA-seq.Methods human menisci were isolated from non-OA patients and OA patients during arthroscopic surgery (N=5). Based on the RNA sequencing, differentially expressed lncRNAs (DELs) and mRNAs (DEMs) were screened.Expression level of selected autophagy-related lncRNAs and mRNAs was validated by real-time qPCR.Results we identified 310 DELs and 320 DEMs, and found five upregulated and one downregulated autophagy-related DEMs. After reverse prediction of miRNA, paired miRNA–lncRNA interactions and verification by RT-qPCR, the ceRNA regulatory networks were constructed consisting of two lncRNAs (PCAT19, CLIP1-ASA) and two mRNAs (BAG3 and HSP90AB1). Finally, GSEA indicated that the increased expressions of autophagy-related mRNAs inhibited the glycosaminoglycan biosynthesis in the degenerative meniscus.Conclusions for the first time ,we constructed an autophagy-related lncRNA-miRNA-mRNA regulatory ceRNA network based on RNA sequencing and experimental validation, which might provide new mechanistic insights and potential therapeutic targets for meniscal degeneration.