<p>Comprehensive Transcriptomic Analysis and Experimental Validation Identify lncRNA HOXA-AS2/miR-184/COL6A2 as the Critical ceRNA Regulation Involved in Low-Grade Glioma Recurrence</p>

Abstract

Purpose: The recurrence and metastasis of glioma are closely related to complex regulatory networks among protein-coding genes, lncRNAs and microRNAs. The aim of this study was to investigate core genes, lncRNAs, miRNAs and critical ceRNA regulatory mechanisms, which are involved in lower-grade glioma (LGG) recurrence. Materials and Methods: We employed multiple datasets from Chinese Glioma Genome Atlas (CGGA) database and The Cancer Genome Atlas (TCGA) to perform comprehensive transcriptomic analysis. Further in vitro experiments including cell proliferation assay, luciferase reporter assay, and Western blot were performed to validate our results. Results: Recurrent LGG and glioblastoma (GBM) showed different transcriptome characteristics with less overlap of differentially expressed protein-coding genes (DEPs), lncRNAs (DELs) and miRNAs (DEMs) compared with primary samples. There were no overlapping gene in ontology (GO) terms related to GBM recurrence in the TCGA and CGGA databases, but there were overlaps associated with LGG recurrence. GO analysis and protein-protein interaction (PPI) network analysis identified three core genes: TIMP1, COL1A1 and COL6A2. By hierarchical cluster analysis of them, LGGs could be clustered as Low_risk and High_risk group. The High_risk group with high expression of TIMP1, COL1A1, and COL6A2 showed worse prognosis. By coexpression networks analysis, competing endogenous RNA (ceRNA) network analysis, cell proliferation assay and luciferase reporter assay, we confirmed that lncRNA HOXA-AS2 functioned as a ceRNA for miR-184 to regulate expression of COL6A2, which induced cell proliferation of low-grade glioma. Conclusion: In this study, we revealed a 3-hub protein-coding gene signature to improve prognostic prediction in LGG, and identified a critical ceRNA regulation involved in LGG recurrence.

NPC2 as a Prognostic Biomarker for Glioblastoma Based on Integrated Bioinformatics Analysis and Cytological Experiments

“…Our result also showed that NPC2 independently indicated unfavorable prognosis in glioma when adjusted for with patents’ age ( p value = 0.04) and alive status ( p value = 0.039) ( Table 1 ), which revealed that NPC2 was a robust independent factor for predicting GBM survival. Considering that age has been identified as prognostic factors for GBM ( Chen P. et al, 2020 ; Hao et al, 2020 ; Zheng et al, 2020 ), NPC2 might be a prognostic marker of GBM based on its significant positive correlation with this disease. Hence, we focus on investing the clinical prognostic significance of the NPC2 genes in GBM.…”

AGAP2-AS1 May Promote the Occurrence and Development of Glioblastoma by Sponging miR-9-5p: Evidence From a ceRNA Network

“…Another study reported that, through the regulation of ADAM12, SP1-mediated upregulation of lncRNA LINC01614 functions as a ceRNA for miR-383, thereby facilitating glioma progression (22). Using a comprehensive transcriptomic analysis and experimental validation, Chen et al identified lncRNA HOXA-AS2/miR-184/COL6A2 as the critical ceRNA regulatory complex involved in low-grade glioma recurrence (23).…”

Long non-coding RNA signatures as predictors of prognosis in thyroid cancer: a narrative review

“…HOXA-AS2 is a novel cancer-related lncRNA that has been demonstrated to be aberrantly expressed in various cancer types (62)(63)(64). In TC, the expression of HOXA-AS2 is upregulated in PTC tissues (65).…”