Abstract | BACKGROUND: 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.
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Authors | Yu Liu, Chunxiang Li, Lingling Fang, Liyu Wang, Hengchang Liu, He Tian, Yujia Zheng, Tao Fan, Jie He |
Journal | Clinical and translational medicine
(Clin Transl Med)
Vol. 12
Issue 6
Pg. e944
(06 2022)
ISSN: 2001-1326 [Electronic] United States |
PMID | 35735113
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2022 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics. |
Chemical References |
- Nuclear Proteins
- RNA, Long Noncoding
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Topics |
- Animals
- Cell Line, Tumor
- Cell Proliferation
(genetics)
- Esophageal Neoplasms
(genetics, pathology)
- Esophageal Squamous Cell Carcinoma
(genetics, metabolism, pathology)
- Gene Expression Regulation, Neoplastic
(genetics)
- Lipid Metabolism
(genetics)
- Mice
- Nuclear Proteins
(genetics, metabolism)
- Obesity
(genetics)
- RNA, Long Noncoding
(genetics, metabolism)
- Tumor Microenvironment
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