Recent evidence has suggested that long non-coding RNAs (lncRNAs) may play a significant role in the pathogenesis of several neurological diseases, including spinal cord injury (SCI). However, little is known about the role of lncRNAs in SCI. The aim of the present study was to evaluate the potential functions of lncRNAs in SCI and to identify the underlying mechanisms of action. We firstly analyzed Gene Expression Omnibus (GEO) datasets to investigate aberrantly-expressed lncRNAs which might be involved in the pathogenesis of SCI. The long non-coding RNA X-inactive specific transcript (XIST) was found to be one of the most significantly upregulated lncRNAs in the GEO dataset analysis, and is associated with apoptosis. We, therefore, selected this as a candidate lncRNA and investigated its function. We found that knockdown of lncRNA-XIST by Lv-shRNA had a prominent protective effect on SCI recovery by suppressing apoptosis through reactivation of the PI3K/AKT signaling pathway in rat spinal cord tissue. In particular, our results suggested that lncRNA-XIST may act as a competitive endogenous RNA, effectively becoming a sink for miR-494, leading to derepression of its target gene, phosphatase and tensin homolog deleted on chromosome ten (PTEN). In addition, an inverse relationship between lncRNA-XIST and miR-494 was observed in spinal cord tissues of SCI rats. Further study demonstrated that antagomiR-494 could reverse the protective effects of lncRNA-XIST knockdown on SCI rats through blocking the PTEN/PI3K/AKT signaling pathway. These results suggested that lncRNA-XIST knockdown may play an important role in limiting neuronal apoptosis in rats following SCI, and that the observed protective effects of lncRNA-XIST knockdown might have been mediated by its regulation on the phosphorylation of AKT by competitively binding miR-494. These findings have revealed, for the first time, the importance of the XIST/miR-494/PTEN/AKT signaling axis in the pathogenesis of SCI and suggest that lncRNA-XIST may be a promising molecular target for SCI therapy.
ObjectLittle is known regarding the anaplastic variant of primary ependymomas that involve the spinal cord. The aim of this study was to evaluate the clinical characteristics and treatment outcomes of primary spinal anaplastic ependymomas (PSAEs).MethodsMedical records were reviewed in 20 patients with pathologically proven PSAEs who underwent surgical treatment at the Department of Neurosurgery in Huashan Hospital between 1999 and 2008.ResultsThis series included 7 women and 13 men between the ages of 2 and 67 years (mean 31.9 years). The mean preoperative course was 9.3 months (range 20 days to 48 months). The most common PSAE locations were the cervical and thoracic spinal cords. The most common presenting symptom was weakness, followed by numbness, bowel or bladder dysfunction, and pain. Gross-total resection (GTR) was achieved in 17 patients, and a subtotal removal was performed in 3 patients. Nine patients received radiation therapy and/or chemotherapy. The mean follow-up duration was 83.5 months. Functional assessment of the 10 patients available at the latest follow-up evaluation showed that 2 had worsened and 8 remained unchanged from their preoperative status. There were 2 local recurrences and 1 lung metastasis.ConclusionsPatients with PSAEs presented with a much shorter preoperative course than patients with Grade II ependymomas in previous studies. Patients with tumors that involved the cervical spinal cord experienced a worse outcome. Surgical removal of PSAEs, with the goal of GTR, is beneficial to patients. The role of radiation therapy and chemotherapy in PSAEs remains to be determined in further studies.
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