Exploring EZH2-Linked lncRNAs in Gastric Cancer: Insights from Sequencing Data and Gene Modulation.

Abstract

Gastric cancer (GC) is one of the leading causes of cancer-related deaths globally. Enhancer of zeste homolog 2 (EZH2), a methyl-transferase and master transcriptional regulator frequently overexpresses in a variety of malignancies. Long non-coding RNAs (lncRNAs) play a significant role in regulating gene expression and are intricately involved in the EZH2 oncogenic regulatory network. We aimed in this study to investigate the expression of EZH2-associated lncRNAs and their probable regulatory role in GC progression. RNA-seq and miRNA-seq data from 375 tumor and 32 normal samples were retrieved from the TCGA database. Differential expression and correlation analyses were performed to identify EZH2-associated lncRNAs. A competing endogenous RNA (ceRNA) network comprising lncRNAs, miRNAs, and mRNAs was constructed and visualized. Functional genomics analysis including EZH2 knockdown and induced overexpression experiments were carried out in AGS and MKN-45 GC cell lines to validate the expression of selected lncRNAs using RT-qPCR. EZH2-correlated analysis revealed 16 upregulated and 8 downregulated lncRNAs with significant associations. EZH2 expression modulation studies confirmed that expression levels of lncRNAs including PVT1, MNX1-AS1, AC103702.2, PCAT7, LINC01235, LINC02086, MIR99AHG, and MAGI2-AS3 were regulated by EZH2 in GC cells. EZH2 modulates the expression of several key lncRNAs associated with gastric cancer progression, suggesting that the EZH2/lncRNA axis could serve as a potential therapeutic target. Targeting this axis may open new avenues for influencing critical molecular pathways involved in GC development.