Analysis of Long Noncoding RNA ZNF667-AS1 as a Potential Biomarker for Diagnosis and Prognosis of Glioma Patients.

OBJECTIVE: Long noncoding RNAs (lncRNAs) have been strongly associated with various types of cancer. The present study aimed at exploring the diagnostic and prognostic value of lncRNA Zinc finger protein 667-antisense RNA 1 (ZNF667-AS1) in glioma patients. Patients and Methods. The expressions of ZNF667-AS1 were detected in 155 glioma tissues and matched normal brain tissue samples by qRT-PCR. The receiver operating characteristic (ROC) curve was performed to estimate the diagnostic value of ZNF667-AS1. The association between the ZNF667-AS1 expression and clinicopathological characteristics was analyzed by the chi-square test. The Kaplan-Meier method was performed to determine the influence of the ZNF667-AS1 expression on the overall survival and disease-free survival of glioma patients. The Cox regression analysis was used to evaluate the effect of independent prognostic factors on survival outcome. Cell proliferation was measured by the respective cell counting Kit-8 (CCK-8) assays. RESULTS: We observed that ZNF667-AS1 was significantly upregulated in glioma tissues compared to normal tissue samples (p < 0.01). Higher levels of ZNF667-AS1 were positively associated with the WHO grade (p = 0.018) and KPS score (p = 0.008). ROC assays revealed that the high ZNF667-AS1 expression had an AUC value of 0.8541 (95% CI: 0.8148 to 0.8934) for glioma. Survival data revealed that glioma patients in the high ZNF667-AS1 expression group had significantly shorter 5-year overall survival (p = 0.0026) and disease-free survival (p = 0.0005) time than those in the low ZNF667-AS1 expression group. Moreover, multivariate analyses confirmed that the ZNF667-AS1 expression was an independent predictor of the overall survival and disease-free survival for glioma patients. Functionally, we found that knockdown of ZNF667-AS1 suppressed the proliferation of glioma cells. CONCLUSIONS: Our results suggest that ZNF667-AS1 could be used as a potential diagnostic and prognostic biomarker in glioma.

Sulforaphane exerts neuroprotective effects via suppression of the inflammatory response in a rat model of focal cerebral ischemia.

Inflammatory damage plays an important role in cerebral ischemic pathogenesis and may represent a promising target for treatment. Sulforaphane exerts protective effects in a rat model of focal cerebral ischemia/reperfusion injury by alleviating brain edema. However, the possible mechanisms of sulforaphane after cerebral ischemia/reperfusion injury have not been fully elucidated. Therefore, in the present study, we investigated the effect of sulforaphane on inflammatory reaction and the potential molecular mechanisms in cerebral ischemia rats. We found that sulforaphane significantly attenuated the blood-brain barrier (BBB) disruption; decreased the levels of pro-inflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-1ß; reduced the nitric oxide (NO) levels and inducible nitric oxide synthase (iNOS) activity; inhibited the expression of iNOS and cyclooxygenase-2 (COX-2). In addition, sulforaphane inhibits the expression of p-NF-κB p65 after focal cerebral ischemia-reperfusion injury. Taken together, our results suggest that sulforaphane suppresses the inflammatory response via inhibiting the NF-κB signaling pathway in a rat model of focal cerebral ischemia, and sulforaphane may be a potential therapeutic agent for the treatment of cerebral ischemia injury.

Effects of small interfering RNA targeting sphingosine kinase-1 gene on the animal model of Alzheimer's disease.

Alzheimer's disease (AD) is an age-related, progressive neurodegenerative disorder that occurs gradually and results in memory, behavior, and personality changes. Abnormal sphingolipid metabolism was reported in AD previously. This study aimed to investigate whether sphK1 could exacerbate the accumulation of amyloid protein (Aß) and sharpen the learning and memory ability of the animal model of AD using siRNA interference. An adenovirus vector expressing small interfering RNA (siRNA) against the sphK1 gene (sphK1-siRNA) was designed, and the effects of sphK1-siRNA on the APP/PS1 mouse four weeks after treatment with sphK1-siRNA hippocampal injection were examined. SphK1 protein expression was confirmed by using Western blotting and ceramide content coupled with S1P secretion was evaluated by enzyme-linked immunosorbent assay (ELISA). Aß load was detected by immunohistochemical staining and ELISA. Morris water maze was adopted to test the learning and memory ability of the APP/PS1 mice. A significant difference in the expression of sphK1 protein and mRNA was observed between the siRNA group and the control group. Aß load in transfected mice was accelerated in vivo, with significant aggravation of the learning and memory ability. The sphK1 gene modulation in the Aß load and the learning and memory ability in the animal model of AD may be important for the treatment of AD.