Gliomas represent 80% of malignant brain tumors. Because of the high heterogeneity, the oncogenic mechanisms in gliomas are still unclear. In this study, we developed a new approach to identify dysregulated competitive endogenous RNA (ceRNA) interactions driven by copy number variation (CNV) in both lower-grade glioma (LGG) and glioblastoma multiforme (GBM). By analyzing genome and transcriptome data from The Cancer Genome Atlas (TCGA), we first found out the protein coding genes and long non-coding RNAs (lncRNAs) significantly affected by CNVs and further determined CNV-driven dysregulated ceRNA interactions by a customized pipeline. We obtained 13,776 CNV-driven dysregulated ceRNA pairs (including 3,954 mRNAs and 306 lncRNAs) in LGG and 262 pairs (including 221 mRNAs and 11 lncRNAs) in GBM, respectively. Our results showed that most of the ceRNA interactions were weakened by CNVs in both LGG and GBM, and many CNV-driven genes shared the same ceRNAs in the dysregulated ceRNA networks. Functional analysis indicated that the CNV-driven ceRNA network involved in some important mechanisms of tumorigenesis, such as cell cycle, p53 signaling pathway and TGF-beta signaling pathway. Further investigation of the ceRNA pairs in the communities from the dysregulated ceRNA network revealed more detailed biological functions related to the oncogenesis of malignant gliomas. Moreover, by exploring the association of CNV-driven ceRNAs with prognosis and histological subtype, we found that the copy number status of MTAP, KLHL9, and ELAVL2 related to the overall survival in LGG and showed high correlation with histological subtype. In conclusion, this study provided new insight into the molecular mechanisms and clinical biomarkers in gliomas.

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.