Background
Obesity alters metabolic microenvironment and is thus associated with several tumours. The
Conclusions
HFD/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.
Methods
A 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.
Results
Palmitic 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. Conclusions: HFD/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.