Comprehensive analysis of prognostic biomarkers in lung adenocarcinoma based on aberrant lncRNA–miRNA–mRNA networks and Cox regression models

Abstract

Lung adenocarcinoma (LUAD) is the leading cause of cancer-related death worldwide, and its underlying mechanism remains unclear. Accumulating evidence has highlighted that long non-coding RNA (lncRNA) acts as competitive endogenous RNA (ceRNA) and plays an important role in the occurrence and development of LUAD. Here, we comprehensively analyzed and provided an overview of the lncRNAs, miRNAs, and mRNAs associated with LUAD from The Cancer Genome Atlas (TCGA) database. Then, differentially expressed lncRNAs (DElncRNA), miRNAs (DEmiRNA), and mRNAs (DEmRNA) were used to construct a lncRNA–miRNA–mRNA regulatory network according to interaction information from miRcode, TargetScan, miRTarBase, and miRDB. Finally, the RNAs of the network were analyzed for survival and submitted for Cox regression analysis to construct prognostic indicators. A total of 1123 DElncRNAs, 95 DEmiRNAs, and 2296 DEmRNAs were identified (|log2FoldChange| (FC) > 2 and false discovery rate (FDR) or adjusted P value < 0.01). The ceRNA network was established based on this and included 102 lncRNAs, 19 miRNAs, and 33 mRNAs. The DEmRNAs in the ceRNA network were found to be enriched in various cancer-related biological processes and pathways. We detected 22 lncRNAs, 12 mRNAs, and 1 miRNA in the ceRNA network that were significantly associated with the overall survival of patients with LUAD (P < 0.05). We established three prognostic prediction models and calculated the area under the 1,3,5-year curve (AUC) values of lncRNA, mRNA, and miRNA, respectively. Among them, the prognostic index (PI) of lncRNA showed good predictive ability which was 0.737, 0.702 and 0.671 respectively, and eight lncRNAs can be used as candidate prognostic biomarkers for LUAD. In conclusion, our study provides a new perspective on the prognosis and diagnosis of LUAD on a genome-wide basis, and develops independent prognostic biomarkers for LUAD.

LINC00514 drives osteosarcoma progression through sponging microRNA-708 and consequently increases URGCP expression

“…Numerous studies have demonstrated that cytoplasmic lncRNAs likely function as competing endogenous RNAs (ceRNAs) to serve as a "sponge/decoy" via miRNA binding and thereby increase miRNA target levels at the post-transcriptional level [25][26][27]. To understand the role of LINC00514 in promoting OS progression, we determined its subcellular localization in HOS and MG-63 cells.…”

Identification of HMG-box family establishes the significance of SOX6 in the malignant progression of glioblastoma

“…We then used DElncRNA, DEmiRNA and DEmRNA in this study to construct lncRNA-miRNA-mRNA associations, as previously reported [18,52]. (1) DElncRNA-DEmiRNA interactions were described by miRcode 11 [53].…”

“…Motifs reported on SOX protein data via MEME v5.0.5 [51]. SOX secondary structure was built by Secondary structure by NPS@: Network Protein Sequence Analysis online service [52].…”

Analysis and construction of a competitive endogenous RNA regulatory network of baicalin-induced apoptosis in human osteosarcoma cells

“…The crosstalk between 2 lncRNAs, 3 miRNAs, and 18 mRNAs revealed a complex mechanism in baicalin-treated MG63 cells. The ceRNA hypothesis explains a new mechanism of RNA interaction and provides important clues and theoretical guidance for further understanding the tumorigenesis mechanism [31] . We observed that lncRNAs sponge several miRNAs, while miRNAs could regulate more than one mRNA.…”

“…The genes with fold-change in expression > 2.0 and P < 0.05 between untreated and baicalin-treated samples were identi ed to be differentially expressed. In total, our project detected 58 lncRNAs, 31…”