Zhang Yichong, Chen Jianhai, He Shengyuan, Xiao Yun, Liu Aiyu, Zhang Dianying, Li Xia
Department of Orthopedics and Trauma, Key Laboratory of Trauma and Neural Regeneration (Ministry of Education/Peking University), Peking University People's Hospital, Beijing, China.
College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang, China.
Front Mol Biosci. 2022 Aug 30;9:940290. doi: 10.3389/fmolb.2022.940290. eCollection 2022.
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. 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. 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-miR-129-5p and hsa-miR-30c-5p, whose interacting mRNAs related to muscle diseases, fat and inflammation. 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.
肩袖撕裂（RCT）是肩部功能障碍最常见的原因，然而，其分子机制仍不清楚。非编码RNA（ncRNA），如长链非编码RNA（lncRNA）、微小RNA（miRNA）和环状RNA（circRNA），参与多种疾病，但它们在RCT中的作用知之甚少。因此，本研究的目的是鉴定失调的ncRNA，并了解它们如何影响RCT。我们对五对撕裂的冈上肌和匹配的未受损肩胛下肌进行了RNA测序和miRNA测序，以鉴定RCT患者中失调的RNA。为了更好地理解基本生物学过程，我们对这些失调的mRNA或失调的ncRNA的共表达基因进行了富集分析。根据竞争性内源性RNA（ceRNA）理论，我们最终建立了ceRNA网络，以探索RCT中失调RNA之间的关系。撕裂的冈上肌和匹配的未受损肩胛下肌之间分别有151个mRNA、38个miRNA、20个lncRNA和90个circRNA差异表达。我们发现这些失调的mRNA、这些失调的miRNA的靶标mRNA或这些失调的ncRNA的共表达mRNA在肌肉结构发育、肌动蛋白介导的细胞收缩和肌动蛋白结合中富集。然后我们构建并分析了ceRNA网络，发现ceRNA网络中最大的模块与血管发育相关。基于最大模块的拓扑特性，我们鉴定了几个重要的ncRNA，包括hsa-miR-129-5p和hsa-miR-30c-5p，其相互作用的mRNA与肌肉疾病、脂肪和炎症有关。本研究对RCT患者的mRNA和ncRNA表达谱进行了系统剖析，揭示了一些可能导致RCT发生的重要ncRNA。这些结果可为RCT的进一步研究提供新的见解。
