Dataset Information

Differential Expression Profiles and Functional Prediction of tRNA-Derived Small RNAs in Rats After Traumatic Spinal Cord Injury.

ABSTRACT: Spinal cord injury (SCI) is mostly caused by trauma. As the primary mechanical injury is unavoidable, a focus on the underlying molecular mechanisms of the SCI-induced secondary injury is necessary to develop promising treatments for patients with SCI. Transfer RNA-derived small RNA (tsRNA) is a novel class of short, non-coding RNA, possessing potential regulatory functions in various diseases. However, the functional roles of tsRNAs in traumatic SCI have not been determined yet. We used a combination of sequencing, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), bioinformatics, and luciferase reporter assay to screen the expression profiles and identify the functional roles of tsRNAs after SCI. As a result, 297 differentially expressed tsRNAs were identified in rats' spinal cord 1 day after contusion. Of those, 155 tsRNAs were significantly differentially expressed: 91 were significantly up-regulated, whereas 64 were significantly down-regulated after SCI (fold change > 1.5; P < 0.05). Bioinformatics analyses revealed candidate tsRNAs (tiRNA-Gly-GCC-001, tRF-Gly-GCC-012, tRF-Gly-GCC-013, and tRF-Gly-GCC-016) that might play regulatory roles through the mitogen-activated protein kinase (MAPK) and neurotrophin signaling pathways by targeting brain-derived neurotrophic factor (BDNF). We validated the candidate tsRNAs and found opposite trends in the expression levels of the tsRNAs and BDNF after SCI. Finally, tiRNA-Gly-GCC-001 was identified to target BDNF using the luciferase reporter assay. In summary, we found an altered tsRNA expression pattern and predicted tiRNA-Gly-GCC-001 might be involved in the MAPK and neurotrophin pathways by targeting the BDNF, thus regulating the post-SCI pathophysiologic processes. This study provides novel insights for future investigations to explore the mechanisms and therapeutic targets for SCI.

SUBMITTER: Qin C

PROVIDER: S-EPMC6968126 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Differential Expression Profiles and Functional Prediction of tRNA-Derived Small RNAs in Rats After Traumatic Spinal Cord Injury.

Qin Chuan C Feng Hao H Zhang Chao C Zhang Xin X Liu Yi Y Yang De-Gang DG Du Liang-Jie LJ Sun Ying-Chun YC Yang Ming-Liang ML Gao Feng F Li Jian-Jun JJ

Frontiers in molecular neuroscience 20200110

Spinal cord injury (SCI) is mostly caused by trauma. As the primary mechanical injury is unavoidable, a focus on the underlying molecular mechanisms of the SCI-induced secondary injury is necessary to develop promising treatments for patients with SCI. Transfer RNA-derived small RNA (tsRNA) is a novel class of short, non-coding RNA, possessing potential regulatory functions in various diseases. However, the functional roles of tsRNAs in traumatic SCI have not been determined yet. We used a combi ...[more]

PMID: 31998075

Similar Datasets

Project description:BackgroundTraumatic spinal cord injury (SCI) is a major clinical concern, and it is a life-changing neurological condition with substantial socioeconomic implications. Muscone has been widely used in traditional Chinese medicinal formulations for its anti-inflammatory activity. However, its protective effects on traumatic SCI have not been explored. This study investigated whether muscone plays a protective role in SCI and compared its effects with those of methylprednisolone sodium succinate (MPSS).MethodsRats were divided into five groups: normal saline (NS; n=24), methylprednisolone (MP; w=24), and muscone 1 (MO1), muscone 2 (MO2), and muscone 3 (MO3) (n=24 in each group, collectively called the MOx groups). The SCI rat model was established by the modified Allen's method. The rats were administered muscone (MO1: 2.5 mg/kg, MO2: 5 mg/kg, and MO3: 10 mg/kg) or MP (30 mg/kg), or an equivalent volume of saline. The rats were kept under observation for 4 weeks. Malondialdehyde (MDA), superoxide dismutase (SOD), interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-alpha (TNF-α) levels were detected using enzyme-linked immunosorbent assay (ELISA). The expression of glial fibrillary acidic protein (GFAP), B-cell lymphoma-2 (BCL-2), and caspase3 was detected by western blot analysis. Hematoxylin-eosin (HE), Nissl, and immunocytochemistry (ICC) staining was performed for pathological observation. Basso-Beattie-Bresnahan motor function scores were evaluated for assessment of neural functions after acute SCI.ResultsMuscone inhibited immune-inflammatory reactions, neuronal necrosis, and apoptosis. The lower limb function recovery was better in the MOx groups compared with NS and MP groups according to Basso-Beattie-Bresnahan scores. The changes were remarkable in the MO2 group compared with the other groups.ConclusionsMuscone alleviates secondary injury after SCI by reducing immune-inflammatory reactions, neuronal necrosis, and apoptosis.

Project description:BackgroundNeurogenic bladder (NB) following suprasacral spinal cord injury (SSCI) is an interstitial disease with the structural remodeling of bladder tissue and matrix over-deposition. Circular RNAs (circRNAs) are involved in fibrotic disease development through their post-transcriptional regulatory functions. This study aimed to use transcriptome high-throughput sequencing to investigate the process of NB and bladder fibrosis after SSCI.MethodsSpinal cord transection at the T10-T11 level was used to construct the SSCI model in rats (10-week-old female Wistar rats, weighing 200 ± 20 g). The bladders were collected without (sham group) and with (SSCI 1-3 groups) NB status. Morphological examination was conducted to assess the extent of bladder fibrosis. Additionally, RNA sequencing was utilized to determine mRNAs and circRNAs expression patterns. The dynamic changes of differentially expressed mRNAs (DEMs) and circRNAs (DECs) in different periods of SSCI were further analyzed.ResultsBladder weight, smooth muscle cell hypertrophy, and extracellular matrix gradually increased after SSCI. Compared with the sham group, 3,255 DEMs and 1,339 DECs, 3,449 DEMs and 1,324 DECs, 884 DEMs, and 1,151 DECs were detected in the SSCI 1-3 groups, respectively. Specifically, circRNA3621, circRNA0617, circRNA0586, and circRNA4426 were significant DECs common to SSCI 1-3 groups compared with the sham group. Moreover, Gene Ontology (GO) enrichment suggested that inflammatory and chronic inflammatory responses were the key events in NB progression following SSCI. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment associated with the "Chemokine signaling pathway", the "IL-17 signaling pathway", and the "TGF-beta signaling pathway" suggests their potential involvement in regulating biological processes. The circRNA-miRNA-mRNA interaction networks of DECs revealed rno-circ-2239 (micu2) as the largest node, indicating that the rno-circ-2239-miRNA-mRNA-mediated network may play a critical role in the pathogenesis of SSCI-induced NB.ConclusionsThis study offers a comprehensive outlook on the possible roles of DEMs and DECs in bladder fibrosis and NB progression following SSCI. These findings have the potential to serve as novel biomarkers and therapeutic targets.

Project description:BackgroundNeurogenic bladder dysfunction represents one of the most common and devastating sequelae of traumatic spinal cord injury (SCI). As early prediction of bladder outcomes is essential to counsel patients and to plan neurourological management, we aimed to develop and validate a model to predict urinary continence and complete bladder emptying 1 y after traumatic SCI.Methods and findingsUsing multivariate logistic regression analysis from the data of 1,250 patients with traumatic SCI included in the European Multicenter Spinal Cord Injury study, we developed two prediction models of urinary continence and complete bladder emptying 1 y after traumatic SCI and performed an external validation in 111 patients. As predictors, we evaluated age, gender, and all variables of the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) and of the Spinal Cord Independence Measure (SCIM). Urinary continence and complete bladder emptying 1 y after SCI were assessed through item 6 of SCIM. The full model relies on lower extremity motor score (LEMS), light-touch sensation in the S3 dermatome of ISNCSI, and SCIM subscale respiration and sphincter management: the area under the receiver operating characteristics curve (aROC) was 0.936 (95% confidence interval [CI]: 0.922-0.951). The simplified model is based on LEMS only: the aROC was 0.912 (95% CI: 0.895-0.930). External validation of the full and simplified models confirmed the excellent predictive power: the aROCs were 0.965 (95% CI: 0.934-0.996) and 0.972 (95% CI 0.943-0.999), respectively. This study is limited by the substantial number of patients with a missing 1-y outcome and by differences between derivation and validation cohort.ConclusionsOur study provides two simple and reliable models to predict urinary continence and complete bladder emptying 1 y after traumatic SCI. Early prediction of bladder function might optimize counselling and patient-tailored rehabilitative interventions and improve patient stratification in future clinical trials.

Project description:Spinal cord injury (SCI) is a serious disorder of the central nervous system with a high disability rate. Long noncoding RNAs (lncRNAs) are reported to mediate many biological processes. The aim of this study was to explore lncRNA and mRNA expression profiles and functional networks after SCI. Differentially expressed genes between SCI model rats and sham controls were identified by microarray assays and analyzed by functional enrichment. Key lncRNAs were identified using a support vector machine- (SVM-) recursive feature elimination (RFE) algorithm. A trans and cis regulation model was used to analyze the regulatory relationships between lncRNAs and their targets. An lncRNA-related ceRNA network was established. We identified 5465 differentially expressed lncRNAs (DE lncRNAs) and 8366 differentially expressed mRNAs (DE mRNAs) in the SCI group compared with the sham group (fold change > 2.0, p < 0.05). Four genes were confirmed by qRT-PCR which were consistent with the microarray data. GSEA analysis showed that most marked changes occurred in pathways related to immune inflammation and nerve cell function, including cytokine-cytokine receptor interaction, neuroactive ligand-receptor interaction, and GABAergic synapse. Enrichment analysis identified 30 signaling pathways, including those associated with immune inflammation response. A total of 40 key lncRNAs were identified using the SVM-RFE algorithm. A key lncRNA-mRNAs coexpression network was generated for 230 951 lncRNA-mRNA pairs with half showing positive correlations. Several key DE lncRNAs were predicted to have "cis"- or "trans"-regulated target genes. The transcription factors, Sp1, JUN, and SOX10, may regulate the interaction between XR_001837123.1 and ETS 1. In addition, five pairs of ceRNA regulatory sequences were constructed. Many mRNAs and lncRNAs were found to be dysregulated after SCI. Bioinformatic analysis showed that DE lncRNAs may play crucial roles in SCI. It is anticipated that these findings will provide new insights into the underlying mechanisms and potential therapeutic targets for SCI.

Dataset Information

Differential Expression Profiles and Functional Prediction of tRNA-Derived Small RNAs in Rats After Traumatic Spinal Cord Injury.

Publications

Differential Expression Profiles and Functional Prediction of tRNA-Derived Small RNAs in Rats After Traumatic Spinal Cord Injury.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets