Sox2ot /miR-9 /Cthrc1 Promote Proliferation and Migration of Schwann Cells Following Nerve Injury.

The effects of traditional treatments for peripheral nerve injury (PNI) are not ideal, which has prompted the identification of new therapeutic strategies. As unique glial cells in the peripheral nervous system, Schwann cells (SCs) play an important role in the repair of PNI. Recent studies have demonstrated that long noncoding RNAs (lncRNAs) are involved in the regulation of nerve repair after PNI. In this study, we used microarray technology to detect mRNA and lncRNA expression profiles at different time points after PNI and identified lncRNA Sox2ot-miR-9-Cthrc1 as a competitive endogenous RNA (ceRNA) for further investigation. Expression of lncRNA Sox2ot was increased after PNI, and overexpression of Sox2ot promoted SCs migration and proliferation. Mechanistic analyses confirmed that Sox2ot can regulate the expression of Cthrc1 through competitive adsorption of miR-9 in SCs, ultimately affecting SCs migration and proliferation. Our findings reveal the key role of lncRNA Sox2ot in nerve regeneration and provide a new direction for PNI treatment.

ADAM10 promotes the proliferation of ligamentum flavum cells by activating the PI3K/AKT pathway.

Ligamentum flavum hypertrophy (LFH) is an important cause of spinal canal stenosis and posterior longitudinal ligament ossification. Although a number of studies have focused on the mechanisms responsible for LFH, the cellular mechanisms remain poorly understood. The aim of the present study was to investigate the roles of differentially expressed genes (DEGs) in LFH, elucidate the mechanisms responsible for LFH and provide a potential therapeutic target for further studies. The GSE113212 dataset was downloaded from the Gene Expression Omnibus (GEO) database. The microarray data were analyzed and DEGs were obtained. Bioinformatics methods, such as Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment and protein­protein interaction (PPI) network analyses were used to obtain the key genes and signaling pathways. In addition, cells derived from hypertrophied ligamentum flavum were cultured, and the key genes and signaling pathways in ligamentum cells were identified through in vitro cell biology and molecular biology experiments. A total of 2,123 genes were screened as DEGs. Among these DEGs, 1,384 genes were upregulated and 739 genes were downregulated. The KEGG pathway analysis revealed that the DEGs were mainly enriched in the PI3K/AKT signaling pathway, and the PPI network analysis screened A disintegrin and metalloproteinase 10 (ADAM10) as a key gene. In vitro experimental verification revealed that ADAM10 promoted the proliferation of ligamentum flavum cells and led to the hypertrophy of the ligamentum by activating the PI3K/AKT pathway. On the whole, the in vitro experimental results suggested that ADAM10 promoted the proliferation of ligamentum flavum cells by activating the PI3K/AKT pathway, which may represent a pathogenic mechanism of LFH. The findings of the present study may provide a basis and direction for further studies on the cellular mechanisms of LFH and present a potential novel therapeutic target and clinical approach.

Inactivation of ICAM1 inhibits metastasis and improves the prognosis of Ewing's sarcoma.

BACKGROUND: Ewing's sarcoma (ES) is a kind of malignant tumor, which often occurs in the long bone, pelvis, and other bone tissues, as well as some soft tissues. It often occurs in children and adolescents, second only to osteosarcoma and rhabdomyosarcoma. In the past 30 years, little progress has been made on the genomic mechanism of ES metastasis. METHODS: The gene expression sequence of ES metastasis samples was compared with that of primary tumor samples to obtain differentially expressed genes (DEGs). Subsequently, we annotated the gene functions and enriched pathways of DEGs. Additionally, the protein and protein interaction network were constructed to screen key genes that can lead to the metastasis in ES. Then, cell and molecular biology experiments were conducted to verify the results obtained from the bioinformatics analysis. Finally, we assessed the correlation of expression between the key genes EWSR and FLI1, and conducted a survival analysis of ICAM1. RESULTS: Our study revealed 153 DEGs. Of these, 82 (53.59%) were upregulated and the remaining 71 (46.41%) were downregulated. The bioinformatics analysis showed that ICAM1 was the key gene leading to the invasion and metastasis of ES. Through cell biology and molecular biology experiments, inactivation of ICAM1 inhibited the metastasis of ES cells. The survival and correlation analyses showed that ICAM1 was a risk factor in patients with ES, and that ICAM1 expression was correlated with EWSR and FLI1 expression. CONCLUSION: Our study shows that inactivation of ICAM1 inhibits metastasis and improves the prognosis of ES. Additionally, our findings provide a better understanding of the underlying mechanisms of metastatic ES, a basis for an accurate diagnosis, and therapeutic targets for ES patients.

Exendin-4 Promotes Schwann Cell Proliferation and Migration via Activating the Jak-STAT Pathway after Peripheral Nerve Injury.

Peripheral nerve injury (PNI) is a common clinical disease that causes the partial loss of segmental exercise and sensory and autonomic nervous function, placing a heavy burden on patients and their families. A previous study confirmed that exendin-4 can effectively improve nerve regeneration and functional recovery after PNI. However, the specific mechanisms by which exendin-4-mediates this repair have not been clarified. To explore the mechanism of exendin-4 in the treatment of PNI, we used microarray analysis to detect gene expression in the distal segment of the sciatic nerve after sciatic injury. Bioinformatics analyses were used to predict the roles of differentially expressed genes (DEGs) in nerve damage repair. Schwann cells (SCs) were cultured, and we verified the molecular mechanism of exendin-4 in SCs and the effect of exendin-4 on peripheral nerve regeneration through in vitro molecular biology and cell biology experiments. In vivo, exendin-4 could significantly promote peripheral nerve regeneration. A total of 180 DEGs between the exendin-4 group and the control group were detected. Bioinformatics analysis indicated that these DEGs were mainly enriched in the Jak-STAT signaling pathway. In vitro, exendin-4 could significantly promote the proliferation and migration of SCs by activating the Jak-STAT pathway, which promoted peripheral nerve regeneration. Our results indicate that exendin-4 promotes SC proliferation, migration and nerve regeneration after PNI by activating the Jak-STAT pathway. Our findings provide a basis and direction for further elucidation of the mechanisms of exendin-4 in the repair of PNI and provide a new way to treat PNI.