Tianyi Chen1,2, Guiyang Wu3, Hai Hu2, Chongshan Wu4. 1. Department of General Surgery, Dalian Medical University, Dalian, China. 2. Center of Gallbladder Disease, Shanghai East Hospital, Institute of Gallstone Disease, Tongji University School of Medicine, Shanghai, China. 3. Department of General Surgery, Taizhou Municipal Hospital Affiliated with Taizhou University, Taizhou, China. 4. Department of General Surgery, Pujiang People's Hospital, Jinhua, China.
Abstract
BACKGROUND: Carnitine palmitoyltransferase 1C (CPT1C) is a critical enzyme that catalyzes carnitinylation of fatty acids for transport into mitochondria for β-oxidation. No previous studies have been conducted to explore the prognostic and oncogenic role of CPT1C in gastric cancer (GC). METHODS: Public RNA-sequencing data and micro-array data were extracted from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases respectively. Survival analysis was performed in TCGA and GSE62254 cohorts. RT-qPCR and Western blot analyses were used to determine genes expression in GC cells. Fatty acid oxidation (FAO) assay kit was used to examine cell FAO rate. The cell proliferation ability and cell cycle were tested by using CCK-8 and cell cycle assay kits. RESULTS: In the both TCGA and GSE62254 cohorts, high expression of CPT1C was significantly associated with poor overall (OS) (P<0.001) and disease free survival (DFS) of GC patients (P<0.001). Silence of CPT1C significantly inhibited cell FAO rate, suppressed cell proliferation and induced cell cycle arrest, while enforced CPT1C expression had the opposite effects. However, etomoxir treatment completely restricted the increase of FAO rate, cell viability and the phase of DNA synthesis caused by enhanced CPT1C expression. Of note, CPT1C expression was transcriptionally activated by hypoxia inducible factor-1α. CONCLUSIONS: High expression of CPT1C induced by hypoxia was closely associated with poor prognosis and can promote proliferation of GC cells. 2020 Journal of Gastrointestinal Oncology. All rights reserved.
BACKGROUND: Carnitine palmitoyltransferase 1C (CPT1C) is a critical enzyme that catalyzes carnitinylation of fatty acids for transport into mitochondria for β-oxidation. No previous studies have been conducted to explore the prognostic and oncogenic role of CPT1C in gastric cancer (GC). METHODS: Public RNA-sequencing data and micro-array data were extracted from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases respectively. Survival analysis was performed in TCGA and GSE62254 cohorts. RT-qPCR and Western blot analyses were used to determine genes expression in GC cells. Fatty acid oxidation (FAO) assay kit was used to examine cell FAO rate. The cell proliferation ability and cell cycle were tested by using CCK-8 and cell cycle assay kits. RESULTS: In the both TCGA and GSE62254 cohorts, high expression of CPT1C was significantly associated with poor overall (OS) (P<0.001) and disease free survival (DFS) of GC patients (P<0.001). Silence of CPT1C significantly inhibited cell FAO rate, suppressed cell proliferation and induced cell cycle arrest, while enforced CPT1C expression had the opposite effects. However, etomoxir treatment completely restricted the increase of FAO rate, cell viability and the phase of DNA synthesis caused by enhanced CPT1C expression. Of note, CPT1C expression was transcriptionally activated by hypoxia inducible factor-1α. CONCLUSIONS: High expression of CPT1C induced by hypoxia was closely associated with poor prognosis and can promote proliferation of GC cells. 2020 Journal of Gastrointestinal Oncology. All rights reserved.
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