Upregulation of LINC00501 by H3K27 acetylation facilitates gastric cancer metastasis through activating epithelial‐mesenchymal transition and angiogenesis

Abstract

BackgroundThe molecular mechanism of the significant role of long noncoding RNAs (lncRNAs) in the progression and metastasis of gastric cancer (GC) remains largely elusive. Our objective is to detect overexpressed lncRNA in GC and investigate its role in promoting epithelial‐mesenchymal transition and tumour microenvironment remodel.MethodsLncRNA differential expression profile in GC was analysed using RNA microarrays. The level of LINC00501 was evaluated in both GC patient tissues and GC cell lines by quantitative reverse transcription PCR and large‐scale (n = 304) tissue microarray. To explore the biological role and regulatory driver of LINC00501 in GC, various experimental techniques including Chromatin isolation by RNA purification (ChIRP), RNA immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP) assay, dual luciferase assays were performed.ResultsClinically, it was observed that LINC00501 level was abnormal overexpression in GC tissue and was associated with GC progression and distant metastasis. Gain and loss molecular biological experiments suggested that LINC00501, promoted EMT process and angiogenesis of GC. Mechanically, the enrichment of H3K27 acetylation in LINC00501 promoter region contributed to the increase of LINC00501 in GC. LINC00501 transactivated transcription of SLUG, by recruiting hnRNPR to its promoter. The growth of GC was inhibited both in vitro and in vivo by suppressing the level of LINC00501 using pharmacological intervention from the histone acetyltransferase (HAT) inhibitor ‐C646.ConclusionsThis study suggests that LINC00501 promotes GC progression via hnRNPR/SLUG pathway, which indicates a promising biomarker and target for GC.

Research progress and applications of epigenetic biomarkers in cancer

“…et al, 2020;Ono et al, 2021). Dou et al (Dou et al, 2023) explained that H3K27 acetylation upregulates LINC00501 to promote gastric cancer metastasis through activation of epithelial-mesenchymal transformation and angiogenesis.…”