Affiliation:
1. Beijing International Science and Technology Cooperation Base of Antivirus Drug, Faculty of Environment and Life,
Beijing University of Technology, Beijing, China
2. Department of Clinical Laboratory, China-Japan Friendship
Hospital, Beijing, China
Abstract
Background:
Although esophageal carcinoma (EC) is one of the most common cancers
in the world, details of its pathogenesis remain unclear. Metabolic reprogramming is a main feature
of EC. Mitochondrial dysfunction, especially the decrease in mitochondrial complex I (MTCI),
plays an important role in the occurrence and development of EC.
Objective:
The objective of the study was to analyze and validate the metabolic abnormalities and
the role of MTCI in esophageal squamous cell carcinoma.
Methods:
In this work, we collected transcriptomic data from 160 esophageal squamous carcinoma
samples and 11 normal tissue samples from The Cancer Genome Atlas (TCGA). The OmicsBean
and GEPIA2 were used to conduct an analysis of differential gene expression and survival in clinical
samples. Rotenone was used to inhibit the MTCI activity. Subsequently, we detected lactate
production, glucose uptake, and ATP production.
Results:
A total of 1710 genes were identified as being significantly differentially expressed. The
Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis
suggested that these differentially expressed genes (DEGs) were significantly enriched in various
pathways related to carcinoma tumorigenesis and progression. Moreover, we further identified
abnormalities in metabolic pathways, in particular, the significantly low expression of multiple
subunits of MTCI genes (ND1, ND2, ND3, ND4, ND4L, ND5, and ND6). Rotenone was used to
inhibit the MTCI activity of EC109 cells, and it was found that the decrease in MTCI activity promoted
HIF1A expression, glucose consumption, lactate production, ATP production, and cell
migration.
Conclusion:
Our results indicated the occurrence of abnormal metabolism involving decreased mitochondrial
complex I activity and increased glycolysis in esophageal squamous cell carcinoma
(ESCC), which might be related to its development and degree of malignancy.
Publisher
Bentham Science Publishers Ltd.
Subject
Organic Chemistry,Computer Science Applications,Drug Discovery,General Medicine