Systematic identification of aberrant non-coding RNAs and their mediated modules in rotator cuff tears

Background: Rotator cuff tears (RCT) is the most common cause of shoulder dysfunction, however, its molecular mechanisms remain unclear. Non-coding RNAs(ncRNAs), such as long ncRNA (lncRNA), microRNA (miRNA) and circular RNA (circRNA), are involved in a variety of diseases, but little is known about their roles in RCT. Therefore, the purpose of this study is to identify dysregulated ncRNAs and understand how they influence RCT. Methods: We performed RNA sequencing and miRNA sequencing on five pairs of torn supraspinatus muscles and matched unharmed subscapularis muscles to identify RNAs dysregulated in RCT patients. To better comprehend the fundamental biological processes, we carried out enrichment analysis of these dysregulated mRNAs or the co-expressed genes of dysregulated ncRNAs. According to the competing endogenous RNA (ceRNA) theory, we finally established ceRNA networks to explore the relationship among dysregulated RNAs in RCT. Results: A total of 151 mRNAs, 38 miRNAs, 20 lncRNAs and 90 circRNAs were differentially expressed between torn supraspinatus muscles and matched unharmed subscapularis muscles, respectively. We found that these dysregulated mRNAs, the target mRNAs of these dysregulated miRNAs or the co-expressed mRNAs of these dysregulated ncRNAs were enriched in muscle structure development, actin-mediated cell contraction and actin binding. Then we constructed and analyzed the ceRNA network and found that the largest module in the ceRNA network was associated with vasculature development. Based on the topological properties of the largest module, we identified several important ncRNAs including hsa_circ_0000722, hsa-miR-129-5p and hsa-miR-30c-5p, whose interacting mRNAs related to muscle diseases, fat and inflammation. Conclusion: This study presented a systematic dissection of the expression profile of mRNAs and ncRNAs in RCT patients and revealed some important ncRNAs which may contribute to the development of RCT. Such results could provide new insights for further research on RCT.