Bioinformatics analysis of potential Key lncRNA-miRNA-mRNA molecules as prognostic markers and important ceRNA axes in gastric cancer

Siqi Tang; Keyong Liao; Yongpeng Shi; Tingting Tang; Beibei Cui; Zunnan Huang

Bioinformatics analysis of potential Key lncRNA-miRNA-mRNA molecules as prognostic markers and important ceRNA axes in gastric cancer

Am J Cancer Res. 2022 May 15;12(5):2397-2418. eCollection 2022.

Authors

Siqi Tang^{1

2}, Keyong Liao^{1

2}, Yongpeng Shi^{1

2}, Tingting Tang¹, Beibei Cui¹, Zunnan Huang^{1

3}

Affiliations

¹ Key Laboratory of Big Data Mining and Precision Drug Design of Guangdong Medical University, Key Laboratory for Research and Development of Natural Drugs of Guangdong Province, School of Pharmacy, Guangdong Medical University Dongguan 523808, Guangdong, China.
² The Second School of Clinical Medicine, Guangdong Medical University Dongguan 523808, Guangdong, China.
³ Marine Medical Research Institute of Guangdong Zhanjiang Zhanjiang 524023, Guangdong China.

PMID: 35693096
PMCID: PMC9185605

Abstract

Gastric cancer (GC), the fifth most common malignancy worldwide, has an extremely poor prognosis at the advanced stage or the early stage if inadequately treated. Long noncoding RNAs (lncRNAs), microRNAs (miRNAs) and mRNAs all function as competing endogenous RNAs (ceRNAs) that target and regulate each other. Changes in their expression and their regulatory bioprocesses play important roles in GC. However, the roles of key RNAs and their regulatory networks remain unclear. In this study, RNA profiles were extracted from The Cancer Genome Atlas database, and R language was used to discover the differentially expressed (DE) lncRNAs, miRNAs and mRNAs in GC. Then, the DERNAs were paired by miRcode, miRDB, TargetScan and DIANA, and the ceRNA network was further constructed and visualized using Cytoscape. Moreover, a functional enrichment analysis was performed using Metascape. Afterward, the "survival" package was employed to identify candidate prognostic targets (DERNA-os) in the ceRNA network. Ultimately, the ceRNA network was analyzed to identify crucial lncRNA/miRNA/mRNA axes. Based on 374 gastric adenocarcinoma and gastric adenoma samples, 283 DEceRNAs (69 lncRNAs, 10 miRNAs, and 204 mRNAs) were identified. The 204 mRNAs were significantly enriched in some interesting functional clusters, such as the trans-synaptic signaling cluster and the protein digestion and absorption cluster. The ceRNA network consisted of 43 ceRNAs (13 lncRNAs, 2 miRNAs, and 28 mRNAs) that were related to prognosis. Among them, 2 lncRNAs (LNC00469 and AC010145.1) and 1 mRNA (PRRT4) were potential new biomarkers. In addition, according to the lncRNA/miRNA/mRNA regulatory relationships among the 43 ceRNAs, we identified four axes that might play important roles in the progression of GC and investigated the potential mechanism of the most promising axis (POU6F2-AS2/hsa-mir-137/OPCML) in promoting the proliferation and invasiveness of GC.

Keywords: Gastric cancer; ceRNA; lncRNA; mRNA; miRNA.