Abstract
BackgroundObesity alters metabolic microenvironment and is thus associated with several tumours. The aim of the present study was to investigate the role, molecular mechanism of action, and potential clinical value of lipid metabolism–related long non‐coding RNA (lncRNA) SLC25A21‐AS1 in oesophageal squamous cell carcinoma (ESCC).MethodsA high‐fat diets (HFDs)‐induced obesity nude mouse model was established, and targeted metabolomics analysis was used to identify critical medium‐long chain fatty acids influencing the growth of ESCC cells. Transcriptomic analysis of public dataset GSE53625 confirmed that lncRNA SLC25A21‐AS1 was a lipid metabolism–related lncRNA. The biological function of lncRNA SLC25A21‐AS1 in ESCC was investigated both in vivo and in vitro. Chromatin immunoprecipitation(ChIP)assay, RNA‐pull down, mass spectrometry, co‐IP, and RNA IP(RIP) were performed to explore the molecular mechanism. Finally, an ESCC cDNA microarray was used to determine the clinical prognostic value of SLC25A21‐AS1 by RT‐qPCR.ResultsPalmitic acid (PA) is an important fatty acid component of HFD and had an inhibitory effect on ESCC cell lines. LncRNA SLC25A21‐AS1 expression was downregulated by PA and associated with the proliferation and migration of ESCC cells in vitro and in vivo. Mechanistically, SLC25A21‐AS1 interacted with nucleophosmin‐1 (NPM1) protein to promote the downstream gene transcription of the c‐Myc in the nucleus. In the cytoplasm, SLC25A21‐AS1 maintained the stability of SLC25A21 mRNA and reduced the intracellular NAD+/NADH ratio by influencing tryptophan catabolism. Finally, we demonstrated that high expression of SLC25A21‐AS1 promoted resistance to cisplatin‐induced apoptosis and was correlated with poor tumour grade and overall survival.ConclusionsHFD/PA has an inhibitory effect on ESCC cells and SLC25A21‐AS1 expression. SLC25A21‐AS1 promotes the proliferation and migration of ESCC cells by regulating the NPM1/c‐Myc axis and SLC25A21 expression. In addition, lncRNA SLC25A21‐AS1 may serve as a favourable prognostic biomarker and a potential therapeutic target for ESCC.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
