Integrated analysis of a ceRNA network reveals potential prognostic lncRNAs in gastric cancer

Abstract

Long noncoding RNAs (lncRNAs) have important biological functions as competing endogenous RNAs (ceRNAs) in tumors, yet the functions and regulatory mechanisms of lncRNA‐related ceRNAs in gastric cancer have not been fully elucidated. In this study, we constructed a lncRNA‐miRNA‐mRNA ceRNA network and identified potential lncRNA biomarkers in gastric cancer. Basing on the RNA profiles downloaded from The Cancer Genome Atlas (TCGA) platform, the gastric cancer‐specific differentially expressed lncRNAs, miRNAs, and mRNAs were screened for constructing a ceRNA network using bioinformatic tools. The enrichment analysis of the biological processes in Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes pathways was performed on the ceRNA‐related DEmRNAs. According to the modularization of protein‐protein interaction (PPI) network, we extracted a ceRNA subnetwork and analyzed the correlation between the expression of the lncRNAs involved and specific clinical features of patients. Next, the expression of highly up‐regulated in liver cancer (HULC) and RP11‐314B1.2 showed significant changes in several pathological processes involved in gastric cancer, and nine lncRNAs were found to be correlated with the overall survival of patients with gastric cancer. Through the univariate and multivariate Cox regression analyses, two lncRNAs (LINC00106 and RP11‐999E24.3) were identified and utilized to establish a risk score model for assessing the prognosis of patients. The analysis results were also partially verified using quantitative real‐time PCR. The findings from this study indicate that HULC, RP11‐314B1.2, LINC00106, and RP11‐999E24.3 could be considered as potential therapeutic targets or prognostic biomarkers in gastric cancer, and provide a new perspective for cancer pathogenesis research.

<p>LncRNA PTCSC3 and lncRNA HULC Negatively Affect Each Other to Regulate Cancer Cell Invasion and Migration in Gastric Cancer</p>

“…[10][11][12][13] Highly upregulated in liver cancer (HULC) is a lncRNA that has been demonstrated as an oncogene involved in many human cancers. [14][15][16] It has been reported that HULC has a high expression level in gastric cancer [17][18][19] and can promote the proliferation, migration and invasion of gastric cancer cells, 20,21 suggesting that HULC plays an important role in pathogenesis of gastric cancer.…”

Regulatory Roles of Related Long Non-coding RNAs in the Process of Atherosclerosis

“…Long non-coding RNAs were previously considered to be "transcription noise" because they show a high degree of tissue specificity and are generally less conservative in evolution (Kornfeld and Brüning, 2014). Other studies have shown that lncRNAs are involved in regulating various physiological and pathological processes (Gu et al, 2019), including genetic imprinting, chromatin modification, epigenetic regulation, the cell cycle, and cell differentiation (Qi et al, 2020). Long non-coding RNAs are now known to be important regulators in gene expression networks because lncRNAs can increase or decrease the stability of mRNA in the cytoplasm, activate or inhibit mRNA translation, and post-translational modification processes, and ultimately affect protein expression.…”

Research progress on long non-coding RNAs and their roles as potential biomarkers for diagnosis and prognosis in pancreatic cancer

“…The lncRNAs can therefore act as a “sponge” and compete with the endogenous target genes for miRNA binding, thereby regulating the downstream mRNA expression levels. This mechanism forms a lncRNA-miRNA-mRNA regulatory network in many cancers [ 26 – 28 ]. In addition to interacting with miRNAs, cytoplasmic lncRNAs can directly bind to mRNAs to stabilize their expression.…”