Integrated Bioinformatics Analysis Reveals ceRNA Triplet Related to Apoptosis in Gastric Cancer

Apoptosis is a form of programmed cell death and evading the apoptosis is a milestone in gastric cancer (GC) tumorigenesis. Various RNAs such as miRNA (microRNA), mRNA (messenger RNA), lncRNA (long non-coding RNA), circRNA (circular RNA), play crucial roles in the apoptosis mechanism. In this present study, we aimed to understand the role played by these RNAs in apoptosis in GC. We constructed a ceRNA (competitive endogenous RNA) network using the expression profiles obtained from SRA (Sequence Read Archive) and GEO (Gene Expression Omnibus) datasets. After network construction, the differentially expressed mRNAs were used for gene prioritization. The prioritized genes and the RNAs interacting with them were analyzed to study their role in GC apoptosis. Then, we performed functional and pathway analysis to understand the role played by these genes in gastric cancer. This resulted in 37 miRNA-mRNA interactions, one miRNA-lncRNA interaction, and 17 miRNA-circRNA interactions. The binding site analysis resulted in 10 miRNAs that share common MRE (miRNA Response Elements) among mRNA, lncRNAs, circRNA. Besides, we found 33 miRNA-mRNA-circRNA and two miRNA-mRNA-lncRNA valid interactions. Integration of multiple omics datasets revealed dysregulated genes, including IGF1, MME, CCND2, CDH2, and COL1A1, implicated in GC apoptosis. Functional enrichment analysis highlighted pathways related to apoptosis, with CCND2 emerging as a key player. The integrative methodology has revealed a new potential diagnostic biomarker for the regulation of gastric cancer (GC) apoptosis: the CCND2-miR-141-3p-hsa_circ_0008035 ceRNA triplet. This discovery offers fresh perspectives into the intricate regulatory pathways governing gene expression in GC, promising significant insights into its pathology.   Received: 6 January 2024 | Revised: 25 April 2024 | Accepted: 10 May 2024   Conflicts of Interest The authors declare that they have no conflicts of interest to this work.   Data Availability Statement The data that support the findings of this study are openly available in NCBI database at https://www.ncbi.nlm.nih.gov/sra; in Gene Expression Omnibus (GEO) at https://www.ncbi.nlm.nih.gov/geo/; in ENCORI from https://academic.oup.com/nar/article/42/D1/D92/1063720?login=false.   Author Contribution Statement Anju R. Nath: Conceptualization, Methodology, Data Curation, Writing – original draft, Visualization. Jeyakumar Natarajan: Writing – review & editing, Supervision.