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Systematic identification of aberrant non-coding RNAs and their mediated modules in rotator cuff tears [mRNA-lncRNA/circRNA]

ABSTRACT: The purpose of this study is to identify dysregulated ncRNAs and understand how they influence Rotator cuff tears (RCT). We performed RNA sequencing and miRNA sequencing on 5 pairs of torn supraspinatus muscles and matched unharmed subscapularis muscles to identify RNAs dysregulated in RCT patients. Based on the results of differential expression analysis and miRNA targeting information, we constructed lncRNA/circRNA-associated dysregulated ceRNA networks in RCT. We found the largest module in the ceRNA network and identified several important ncRNAs in this module, which may have critical roles in RCT.

ORGANISM(S): Homo sapiens

PROVIDER: GSE199484 | GEO | 2022/04/21

REPOSITORIES: GEO

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Project description:Background Rotator cuff tears (RCT) is a common musculoskeletal disorder in the shoulder which cause pain and functional disability. Diabetes mellitus (DM) is characterized by impaired ability of producing or responding to insulin and has been reported to act as a risk factor of the progression of rotator cuff tendinopathy and tear. Long non-coding RNAs (lncRNAs) are involved in the development of various diseases, but little is known about their potential roles involved in RCT of diabetic patients. Methods RNA-Sequencing (RNA-Seq) was used in this study to profile differentially expressed lncRNAs and mRNAs in RCT samples between 3 diabetic and 3 nondiabetic patients. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis were performed to annotate the function of the differentially expressed genes (DEGs). LncRNA-mRNA co-expression network and competing endogenous RNA (ceRNA) network were constructed to elucidate the potential molecular mechanisms of DM affecting RCT. Results In total, 505 lncRNAs and 388 mRNAs were detected to be differentially expressed in RCT samples between diabetic and nondiabetic patients. GO functional analysis indicated that related lncRNAs and mRNAs were involved in metabolic process, immune system process and others. KEGG pathway analysis indicated that related mRNAs were involved in ferroptosis, PI3K-Akt signaling pathway, Wnt signaling pathway, JAK-STAT signaling pathway and IL-17 signaling pathway and others. LncRNA-mRNA co-expression network was constructed, and ceRNA network showed the interaction of differentially expressed RNAs, comprising 5 lncRNAs, 2 mRNAs, and 142 miRNAs. TF regulation analysis revealed that STAT affected the progression of RCT by regulating the apoptosis pathway in diabetic patients. Conclusions We preliminarily dissected the differential expression profile of lncRNAs and mRNAs in torn rotator cuff tendon between diabetic and nondiabetic patients. And the bioinformatic analysis suggested some important RNAs and signaling pathways regarding inflammation and apoptosis were involved in diabetic RCT. Our findings offer a new perspective on the association between DM and progression of RCT.

Project description:PurposeTo determine whether anterior cable tears could be identified at the time of arthroscopic rotator cuff repair and determine the characteristics of the anterior cable tears identified.MethodsFrom 2016 to 2017 all shoulder arthroscopies had data collected prospectively at the time of surgery, specifically including injury to the capsular and tendon zones of insertion on the greater tuberosity. Anterior cable position and degree of injury and medialization were recorded, as well as complete findings of the diagnostic arthroscopy. The inclusion criterion was primary shoulder arthroscopy. The exclusion criterion was any revision shoulder arthroscopy. All arthroscopic rotator cuff repairs (ARCR) were grouped together and all other nonarthroscopic rotator cuff repair surgeries (non-ARCR) were grouped together.ResultsIn total, 118 shoulder arthroscopies had data collected prospectively at the time of surgery: 90 primary shoulder arthroscopies met the inclusion criteria; 28 were excluded because they were revision surgeries. There were 42 patients in the ARCR group (Group 1). Six of these were partial tears, and 36 were full-thickness tears. There were 48 patients in the non-ARCR group (Group 2). The non-ARCR Group 2 served as an anatomic baseline for ARCR Group 1. In all 90 shoulders, the rotator cable and anterior cable were identified. Group 1 (ARCR) incidence of anterior cable tears with abnormal position was 71.4% compared to 2.1% in group 2 (non-ARCR) (P < .001) Group 1 (ARCR) incidence of anterior cable tears with normal anterior cable position (n = 12) was compared to abnormal anterior cable position (n = 30). Injury to the anterior footprint capsular and tendon zones were compared. Normal anterior cable position correlated with no or low-grade injury to anterior footprint capsular zone. (Nimura zone C1). Abnormal anterior cable displacement graded as moderate (n = 20) and severe (n = 10) were compared for injury to the anterior footprint. Moderate displacement correlated with complete or high grade injury to C1 in 85% and complete injury to R1 in 45% (P < .001 and .049). In severe displacement complete C1 injury was 100%, and complete R1 injury was 100% (P < .001 and .001).ConclusionsAnterior cable tears are universally identified in ARCR. Three patterns of medial displacement severity correlated with injury to a crucial insertion zone (C1) at the anterior footprint. The degree of anterior cable disruption at the anterior footprint and displacement was commonly disproportionately greater than the injury to the supraspinatus.Level of evidenceLevel III, diagnostic study.

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Systematic identification of aberrant non-coding RNAs and their mediated modules in rotator cuff tears [mRNA-lncRNA/circRNA]

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