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

Abstract

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.

Analysis of differentially expressed genes in torn rotator cuff tendon tissues in diabetic patients through RNA-sequencing

“…Based on the competing endogenous RNA (ceRNA) hypothesis, lncRNAs can regulate the expression of mRNAs through acting as molecular sponges of miRNAs [ 1 ]. A series of studies have explored the lncRNAs-miRNAs-mRNAs interactions in RCT [ 1 , 18 ].…”

“…Based on the competing endogenous RNA (ceRNA) hypothesis, lncRNAs can regulate the expression of mRNAs through acting as molecular sponges of miRNAs [ 1 ]. A series of studies have explored the lncRNAs-miRNAs-mRNAs interactions in RCT [ 1 , 18 ]. In this study, a ceRNA network was constructed to investigate potential interactions among lncRNAs, mRNAs, and miRNAs (Fig.…”

“…Based on their results, they found that lncRNA‑COL6A4P2, A2MP1 and LOC100996671 may act as a regulator in the process of the inflammation of LHBT in RCT patients through NFKB2/NF‑kappa B signaling pathway. Furthermore, Zhang et al [ 1 ] comprehensively dissected the dysregulated transcriptome of RCT, including mRNAs, miRNAs, lncRNAs, and circRNAs. They constructed the lncRNA/circRNA-associated dysregulated ceRNA networks and identified several important ncRNAs among it (hsa_circ_0000722, hsa-miR-129-5p and hsa-miR-30c-5p).…”

“…Zhang et al [ 1 ] has reported that several miRNAs, such as hsa-miR-129-5p and hsa-miR-30c-5p which were dysregulated in inflammation-related diseases, may involve in inflammatory response in RCT. In our study, hsa-miR-5787 was one of the miRNAs identified in ceRNA network.…”

“…Rotator cuff tears (RCT), usually caused by trauma and degeneration of the tendon tissue, is the leading cause of pain and functional disability of the shoulder [ 1 ]. The prevalence of RCT reaches to at least 10% among people over 60 years, which will leave a serious clinical problem in modern society [ 2 ].…”