Construction of lncRNA-associated ceRNA networks to identify prognostic lncRNA biomarkers for glioblastoma.

Long noncoding RNAs (lncRNAs) serve as competitive endogenous RNAs (ceRNAs) that play significant regulatory roles in the pathogenesis of tumors. However, the role of lncRNAs, especially the lncRNA-related ceRNA regulatory network, in glioblastoma (GBM) has not been fully elucidated. The goal of the current study was to construct lncRNA-microRNA-mRNA-related ceRNA networks for further investigation of their mechanism of action in GBM. We downloaded data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases and identified differential lncRNAs, microRNAs (miRNAs), and messenger RNAs (mRNAs) associated with GBM. A ceRNA network was constructed and analyzed to examine the relationship between lncRNAs and patients' overall survival. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGGs) were used to analyze the related mRNAs to indirectly explain the mechanism of action of lncRNAs. The potential effective drugs for the treatment of GBM were identified using the connectivity map (CMap). After integrated analysis, we obtained a total of 210 differentially expressed lncRNAs, 90 differentially expressed miRNAs, and 2508 differentially expressed mRNAs (DEmRNAs) from the TCGA and GEO databases. Using these differential genes, we constructed a lncRNA-associated ceRNA network. Six lncRNAs in the ceRNA network were associated with the overall survival of patients with GBM. Through KEGG analysis, it was found that the DEmRNAs involved in the network are related to cancer-associated pathways, for instance, mitogen-activated protein kinase and Ras signaling pathways. CMap analysis revealed four small-molecule compounds that could be used as drugs for the treatment of GBM. In this study, a multi-database joint analysis was used to construct a lncRNA-related ceRNA network to help identify the regulatory functions of lncRNAs in the pathogenesis of GBM.

Liu Z ，Wang X ，Yang G ，Zhong C ，Zhang R ，Ye J ，Zhong Y ，Hu J ，Ozal B ，Zhao S ... -  《-》

Construction and comprehensive analysis of a competitive endogenous RNA network to reveal potential biomarkers for the malignant differentiation of glioma.

Long noncoding RNAs (lncRNAs) can act as microRNA (miRNA) sponges to regulate protein-coding gene expression; therefore, lncRNAs are considered major components of the competitive endogenous RNA (ceRNA) network and have attracted growing attention. This study explored the regulatory mechanisms and functional roles of lncRNAs as ceRNAs in the malignant differentiation of low-grade glioma (LGG) to glioblastoma (GBM) and their potential impact on the prognosis of patients with GBM. LncRNA and messenger RNA (mRNA) data were extracted from the Cancer Genome Atlas (TCGA) database from 156 GBM samples and 529 LGG samples. Separately, the miRNA expression data were downloaded from the Gene Expression Omnibus database, with the GSE112009 dataset containing miRNA expression data from 10 GBM samples and 15 LGG samples. Weighted gene coexpression network analysis was performed to screen the glioma grade-related lncRNAs. Then, a ceRNA network was established. The database for annotation, visualization, and integrated discovery was adopted to conduct functional enrichment analysis based on 57 upregulated differentially expressed mRNAs in the ceRNA network. Finally, Kaplan-Meier curves were created for the survival analysis of 13 hub lncRNA by combining the clinical data of GBM patients in TCGA. A ceRNA network including 16 lncRNAs, 18 miRNAs, and 78 mRNAs specific to the malignant differentiation of LGG to GBM was established. The 57 upregulated differentially expressed mRNAs in the ceRNA network were significantly enriched in 35 gene ontology terms and 5 pathways. The survival analysis showed that 2 lncRNAs (LINC00261 and HOXA10-AS) were prognostic biomarkers for patients with GBM in TCGA. The proposed ceRNA network may help elucidate the regulatory mechanism by which lncRNAs function as ceRNAs and contribute to the malignant differentiation of LGG to GBM. Importantly, the candidate lncRNAs, miRNAs, and mRNAs involved in the ceRNA network can be further evaluated as potential therapeutic targets and prognostic biomarkers for GBM.

Li X ，Zhang J ，Zhang M ，Qi X ，Wang S ，Teng J ... -  《-》

Identification and functional characterization of lncRNAs acting as ceRNA involved in the malignant progression of glioblastoma multiforme.

Zhang K ，Li Q ，Kang X ，Wang Y ，Wang S ... -  《-》

Comprehensive analysis of differentially expressed profiles of lncRNAs, mRNAs, and miRNAs in laryngeal squamous cell carcinoma in order to construct a ceRNA network and identify potential biomarkers.

This study aimed to uncover a regulatory network comprised of long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs) in laryngeal squamous cell carcinoma (LSCC), to explore its underlying mechanisms and development, and to identify key genetic biomarkers for the prognosis of LSCC. Here, we compared mRNA, lncRNA, and miRNA expression profiles between 111 LSCC and 12 adjacent normal tissues using RNA sequencing (RNA-Seq) data from the Cancer Genome Atlas (TCGA) database. Based on the interaction information obtained from miRcode, TargetScan, miRTarBase, and miRDB, a lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) network was constructed using differentially expressed lncRNAs (DElncRNA), miRNAs (DEmiRNA), and mRNAs (DEmRNA). By assessing the functional enrichment of DEmRNAs in this network, the potential underlying mechanisms were explored. In addition, Kaplan-Meier survival analysis was used to assess genetic biomarkers related to the prognosis of LSCC patients. Upon comparing LSCC and control tissues, 1640 DElncRNAs, 75 DEmiRNAs, and 3217 DEmRNAs were identified. Based on the prediction between lncRNA-miRNA and miRNA-mRNA relationships, we constructed a ceRNA network comprised of 93 lncRNAs, nine miRNAs, and nine mRNAs. This network predicted that two lncRNAs (AC016773.1 and C00299), two mRNAs (DIO1 and STC2), and two miRNAs (hsa-mir-137 and hsa-mir-210) were significant biomarkers of LSCC prognosis according to thorough topological and survival analyses (P < .05). Through a ceRNA network analysis, our study identifies new lncRNAs, miRNAs, and mRNAs, which can be used as potential biomarkers of LSCC and as therapeutic targets for treating LSCC, thus laying a foundation for future clinical studies.

Kong X ，Qi J ，Yan Y ，Chen L ，Zhao Y ，Fang Z ，Fan J ，Liu M ，Liu Y ... -  《-》

Comprehensive analysis of lncRNA-associated ceRNA network reveals novel potential prognostic regulatory axes in glioblastoma multiforme.

Bazrgar M ，Mirmotalebisohi SA ，Ahmadi M ，Azimi P ，Dargahi L ，Zali H ，Ahmadiani A ... -  《-》