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Abstract Background Long non-coding RNAs (lncRNAs) have been considered as one type of gene expression regulator for cancer development, but it is not clear how these are regulated. This study aimed to identify a specific lncRNA that promotes glioma progression. Methods RNA sequencing (RNA-seq) and quantitative real-time PCR were performed to screen differentially expressed genes. CCK-8, transwell migration, invasion assays, and a mouse xenograft model were performed to determine the functions of TMEM44-AS1. Co-IP, ChIP, Dual-luciferase reporter assays, RNA pulldown, and RNA immunoprecipitation assays were performed to study the molecular mechanism of TMEM44-AS1 and the downstream target. Results We identified a novel lncRNA TMEM44-AS1, which was aberrantly expressed in glioma tissues, and that increased TMEM44-AS1 expression was correlated with malignant progression and poor survival for patients with glioma. Expression of TMEM44-AS1 increased the proliferation, colony formation, migration, and invasion of glioma cells. Knockdown of TMEM44-AS1 in glioma cells reduced cell proliferation, colony formation, migration and invasion, and tumor growth in a nude mouse xenograft model. Mechanistically, TMEM44-AS1 is directly bound to the SerpinB3, and sequentially activated Myc and EGR1/IL-6 signaling; Myc transcriptionally induced TMEM44-AS1 and directly bound to the promoter and super-enhancer of TMEM44-AS1, thus forming a positive feedback loop with TMEM44-AS. Further studies demonstrated that Myc interacts with MED1 regulates the super-enhancer of TMEM44-AS1. More importantly, a novel small-molecule Myc inhibitor, Myci975, alleviated TMEM44-AS1-promoted the growth of glioma cells. Conclusions Our study implicates a crucial role of the TMEM44-AS1-Myc axis in glioma progression and provides a possible anti-glioma therapeutic agent.

Glioma is well known as the most aggressive and prevalent primary malignant tumor in the central nervous system. Molecular subtypes and prognosis biomarkers remain a promising research area of gliomas. Notably, the aberrant expression of mesenchymal (MES) subtype related long non-coding RNAs (lncRNAs) is significantly associated with the prognosis of glioma patients. In this study, MES-related genes were obtained from The Cancer Genome Atlas (TCGA) and the Ivy Glioblastoma Atlas Project (Ivy GAP) data sets of glioma, and MES-related lncRNAs were acquired by performing co-expression analysis of these genes. Next, Cox regression analysis was used to establish a prognostic model, that integrated ten MES-related lncRNAs. Glioma patients in TCGA were divided into high-risk and low-risk groups based on the median risk score; compared with the low-risk groups, patients in the high-risk group had shorter survival times. Additionally, we measured the specificity and sensitivity of our model with the ROC curve. Univariate and multivariate Cox analyses showed that the prognostic model was an independent prognostic factor for glioma. To verify the predictive power of these candidate lncRNAs, the corresponding RNA-seq data were downloaded from the Chinese Glioma Genome Atlas (CGGA), and similar results were obtained. Next, we performed the immune cell infiltration profile of patients between two risk groups, and gene set enrichment analysis (GSEA) was performed to detect functional annotation. Finally, the protective factors DGCR10 and HAR1B, and risk factor SNHG18 were selected for functional verification. Knockdown of DGCR10 and HAR1B promoted, whereas knockdown of SNHG18 inhibited the migration and invasion of gliomas. Collectively, we successfully constructed a prognostic model based on a ten MES-related lncRNAs signature, which provides a novel target for predicting the prognosis for glioma patients.