Abstract
Objective Accumulating evidence implies that long noncoding RNAs (lncRNAs) play a crucial role in predicting survival for glioma patients. However, the potential function of lncRNA ELF3-antisense RNA 1 (ELF3-AS1) in tumors remained largely unclear. The aim of this study was to explore the expression of lncRNA ELF3-antisense RNA 1 (ELF3-AS1) and evaluate its functions in glioma patients. Patients and Methods. ELF3-AS1 expressions were examined by RT-PCR in 182 pairs of glioma specimens and adjacent normal tissues. The receiver operating characteristic (ROC) curve was performed to estimate the diagnostic value of ELF3-AS1. The chi-square tests were used to examine the associations between ELF3-AS1 expression and the clinicopathological characters. The overall survival (OS) and disease-free survival (DFS) were analyzed by log-rank test, and survival curves were plotted according to Kaplan-Meier. The prognostic value of the ELF3-AS1 expression in glioma patients was further analyzed using univariate and multivariate Cox regression analyses. Loss-of-function assays were performed to determine the potential function of ELF3-AS1 on the proliferation and invasion of glioma cells. Results The ELF3-AS1 expression level was significantly higher in glioma specimens compared with adjacent nontumor specimens (p < 0.01). A high expression of ELF3-AS1 was shown to be associated with the WHO grade (p = 0.023) and KPS score (p = 0.012). ROC assays revealed that high ELF3-AS1 expression had an AUC value of 0.8073 (95% CI: 0.7610 to 0.8535) for glioma. Using the Kaplan-Meier analysis, we found that patients with a high ELF3-AS1 expression had significantly poor OS (p = 0.006) and DFS (p = 0.0002). In a multivariate Cox model, we confirmed that ELF3-AS1 expression was an independent poor prognostic factor for glioma patients. The functional assay revealed that knockdown of ELF3-AS1 suppressed the proliferation and invasion of glioma cells. Conclusions Our findings confirmed that ELF3-AS1 functions as an oncogene in glioma and indicated that ELF3-AS1 is not only an important prognostic marker but also a potential therapy target for glioma.
Highlights
Glioma is a common malignant primary brain tumor in adults and accounts for 35% of all central nervous systemrelated tumors as well as 85% of all primary malignant brain tumors[1, 2]
To determine whether ELF3-AS1 was abnormally expressed in glioma, qRT-PCR assisted in examining the ELF3-AS1 expression exhibited by 182 pairs of glioma tissues as well as the noncancerous tissues
We observed that the glioma specimens with advanced stages exhibited a higher level of ELF3-AS1 than those with early stages (Figure 1(b))
Summary
Glioma is a common malignant primary brain tumor in adults and accounts for 35% of all central nervous systemrelated tumors as well as 85% of all primary malignant brain tumors[1, 2]. New biological therapies have made progression with regard to the therapeutic intervention, including chemotherapy, radiotherapy, glioma surgery, gene therapy, and immunotherapy, glioma patients’ overall survival (OS) is only 10-15 months after diagnosis[5,6,7]. It is necessary to develop new strategies for diagnosing and treating glioma, thereby reducing the recurrence as well as improving the OS. Long noncoding RNAs (lncRNAs) are long RNA transcripts (>200 nucleotides) that do not possess proteincoding capabilities[8]. Different from short noncoding RNAs, lncRNAs exhibited an underestimated function role because of initially being identified as the transcriptional noise in the genome[9, 10]. Growing studies have indicated that lncRNAs participate in various biological activities, like cell differentiation, apoptosis, and gene expression epigenetic
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