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The tsRNAs (tRNA-derived small RNAs) are new types of small noncoding RNAs derived from tRNAs. Gliomas are well-known malignant brain tumors. The study focused on tsRNA characterizations within gliomas. Datasets processing, bioinformatics analyses, and visualizations were performed with the packages of Python and R. Cell proliferations were demonstrated via CCK8 assays and colony formation assays, and in vivo xenograft experiments. Dual-luciferase reporter assay was performed to confirm the binding of tsRNA with its targets. Via using bioinformatics approaches, the hundreds of tsRNAs with available expression abundance were identified in gliomas dataset, most of them derived from D-loop or T-loop fragments of tRNAs. Among tsRNAs derived from tRNA-Cys-GCA, tRFdb-3003a and tRFdb-3003b (tRFdb-3003a/b) were remarkably down-regulated in gliomas. The survival outcome of gliomas patients with low tRFdb-3003a/b expressions was notably worse than that of high-expression patients. In glioma cells, tRFdb-3003a could suppress cells proliferation and colony formation ability. In vivo , tRFdb-3003a suppressed the tumor growth of xenograft gliomas. Enrichment analyses displayed the tRFdb-3003a-related mRNAs were enriched in the specific GO terms, spliceosome and autophagy pathways, and three GSEA molecular signatures. Mechanically, 3'-UTR regions of VAV2 mRNA were predicted to contain the binding positions of tRFdb-3003a/b, tRFdb-3003a and tRFdb-3003b was effective to reduce the relative luciferase activity of cells with VAV2 wild-type reporter. Overexpression of tRFdb-3003a/b could down-regulated the expression levels of VAV2 protein and mRNA in glioma cells. The tRNA-Cys-GCA derived tRFdb-3003a and tRFdb-3003b might act as key player in tumor progressions of gliomas; tRFdb-3003a/b might directly bind to VAV2 and regulate VAV2 expressions in gliomas., Competing Interests: The authors have declared no conflicting interests., (Copyright © 2022 Jian Ren et al.)

Cerebral ischemia causes hypoxic injury and inflammation, and brain microvascular endothelial cells (BMVECs) dysfunction is an initial stage of blood-brain barrier disruption. Endothelial cells secrete extracellular vesicles (EVs) that are involved in intercellular signal transduction. EVs contain a variety of RNAs, proteins, and metabolites. Circular RNA (circRNA) is a member of the non-coding RNA. The expression profile and potential function of circRNAs in BMVECs are unknown. Here, human BMVECs have undergone hypoxia or TNF-α induction, and the changes in circRNAs were measured by RNA sequencing. A total of 70 circRNAs showed differential expression, including 43 previously unrecorded circRNAs and 27 recorded circRNAs. Since astrocyte end-feet encircle endothelial cells, they are considered the main targets of the EVs from BMVEC. The miRNA sequence data and bioinformatics were used to predict the circRNA-miRNA-mRNA networks in astrocytes. The gene ontology (GO) analysis showed the main downstream targets of circRNAs are DNA transcription regulation and protein kinase-related signaling pathways. These results suggest that altering circRNAs may be a potential therapeutic target for cerebral ischemia induced hypoxic injury and inflammation., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Neuroregeneration and apoptosis are two important pathophysiologic changes after spinal cord injury (SCI), but their underlying mechanisms remain unclear. MicroRNAs (miRNAs) play a crucial role in the regulation of neuroregeneration and neuronal apoptosis, research areas that have been greatly expanded in recent years. Here, using miRNA arrays to profile miRNA transcriptomes, we demonstrated that miR-127-3p was significantly down-regulated after spinal cord transection (SCT). Then, bioinformatics analyses and experimental detection showed that miR-127-3p exhibited specific effects on the regulation of neurite outgrowth and the induction of neuronal apoptosis by regulating the expression of the mitochondrial membrane protein mitoNEET. Moreover, knockdown of MitoNEET leaded to neuronal loss and apoptosis in primary cultured spinal neurons. This study therefore revealed that miR-127-3p, which targets mitoNEET, plays a vital role in regulating neurite outgrowth and neuronal apoptosis after SCT. Thus, modificatioin of the mitoNEET expression, such as mitoNEET activition may provide a new strategy for the treatment of SCI in preclinical trials.

Acetylcholine receptors (AChRs) serve as connections between motor neurons and skeletal muscle and are essential for recovery from spinal cord transection (SCT). Recently, microRNAs have emerged as important potential biotherapeutics for several diseases; however, whether miRNAs operate in the modulation of AChRs remains unknown. We found increased AChRs numbers and function scores in rats with SCT; these increases were reduced following the injection of a eukaryotic translation initiation factor 5A1 (eIF5A1) shRNA lentivirus into the hindlimb muscle. Then, high-throughput screening for microRNAs targeting eIF5A1 was performed, and miR-434-3p was found to be robustly depleted in SCT rat skeletal muscle. Furthermore, a highly conserved miR-434-3p binding site was identified within the mRNA encoding eIF5A1 through bioinformatics analysis and dual-luciferase assay. Overexpression or knockdown of miR-434-3p in vivo demonstrated it was a negative post-transcriptional regulator of eIF5A1 expression and influenced AChRs expression. The microarray-enriched Gene Ontology (GO) terms regulated by miR-434-3p were muscle development terms. Using a lentivirus, one functional gene (map2k6) was confirmed to have a similar function to that of miR-434-3p in GO terms. Finally, HRM and MeDIP-PCR analyses revealed that DNA demethylation also up-regulated eIF5A1 after SCT. Consequently, miR-434-3p/eIF5A1 in muscle is a promising potential biotherapy for SCI repair.

Spinal cord injury (SCI) often results in motor disability concomitant with limit neuroplasticity; the underlying mechanism, however, is still unclear. This study established spinal cord transection rats model (T10), then performed cDNA microarray analysis and found that vimentin located in astrocytes was increased significantly in scar tissues after transection. To understand the role of vimentin and it's mechanism of regulation, RNA interference and luciferase assay were used. Vimentin knockdown in the scar tissues showed a significant improvement on locomotor function in hindlimbs, while vimentin overexpression exhibited an opposite effect. In vitro, vimentin downregulation or overexpression can effectively inhibit or increase astrogliosis, respectively. Moreover, by using biological informatics technology, we predicted that vimentin may be as the target of micRNA138 (miR-138), and confirmed that miR-138 could regulate vimentin by luciferase activity assay. The present results not only validated the exact role of vimentin in transected spinal cord, but also exhibited a novel regulation mechanism, in which miR-138 may regulate vimentin to promote neuroplasticity. It, therefore, provides a novel target for gene drug discovery based on miRNA-138 or vimentin for the treatment of SCI in the future clinic trial.