https://orcid.org/0000-0003-0965-6818
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ABSTRACT
Keratin 80 (KRT80) is a filament protein that makes up one of the major structural fibers of epithelial cells, and involved in cell differentiation and epithelial barrier integrity. Here, KRT80 mRNA expression was found to be higher in esophageal cancer than normal epithelium by RT-PCR and bioinformatics analysis (p < .05), opposite to KRT80 methylation (p < .05). There was a negative relationship between promoter methylation and expression level of KRT80 gene in esophageal cancer (p < .05). KRT80 mRNA expression was positively correlated with the differentiation, infiltration of immune cells, and poor prognosis of esophageal cancer (p < .05). KRT80 mRNA expression was positively linked to no infiltration of immune cells, the short survival time of esophageal cancers (p < .05). The differential genes of KRT80 mRNA were involved in fat digestion and metabolism, peptidase inhibitor, and intermediate filament, desosome, keratinocyte differentiation, epidermis development, keratinization, ECM regulator, complement cascade, metabolism of vitamins and co-factor (p < .05). KRT-80-related genes were classified into endocytosis, cell adhesion molecule binding, cadherin binding, cell–cell junction, cell leading edge, epidermal cell differentiation and development, T cell differentiation and receptor complex, plasma membrane receptor complex, external side of plasma membrane, metabolism of amino acids and catabolism of small molecules, and so forth (p < .05). KRT80 knockdown suppressed anti-apoptosis, anti-pyroptosis, migration, invasion, chemoresistance, and lipogenesis in esophageal cancer cells (p < .05), while ACC1 and ACLY overexpression reversed the inhibitory effects of KRT80 on lipogenesis and chemoresistance. These findings indicated that up-regulated expression of KRT80 might be involved in esophageal carcinogenesis and subsequent progression, aggravate aggressive phenotypes, and induced chemoresistance by lipid droplet assembly and ACC1- and ACLY-mediated lipogenesis.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Authors’ contributions
ZHC designed and organized the project. LJ and YNC collected the samples of esophageal cancer. YWJ and ZCY performed the experiments. ZHC analyzed the data and contributed to the manuscript writing. CZG and ZL helped to revise the draft.
Data availability statement
The datasets used and/or analyzed are available from the corresponding author on reasonable request.
Supplementary material
Supplemental data for this article can be accessed online at https://doi.org/10.1080/15384047.2024.2302162
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Funding
Notes on contributors
Wen-Jing Yun
Wen-Jing Yun, master’s degree, graduated from Jilin University and now works in the Department of Oncology of the Affiliated Hospital of Chengde Medical University, mainly focuses on tumor biomarker research.
Jun Li
Jun Li, chief physician, MD, graduated from China Medical University, now works in Shandong First Medical University Affiliated Provincial Hospital. He is mainly engaged in the clinical treatment and basic research of thoracic tumors, especially in the multidisciplinary treatment of lung cancer and esophageal cancer.
Nan-Chang Yin
Nan-Chang Yin, Chief Physician, graduated from Jinzhou Medical University and is currently employed at the First Affiliated Hospital of Jinzhou Medical University, in the Department of Cardiothoracic Surgery. Specializes in the diagnosis and treatment of coronary heart disease, heart valve disease, aortic disease, lung cancer, esophageal cancer, and other related illnesses. Particularly adept at treating chest diseases using thoracoscopic techniques.
Cong-Yu Zhang
Cong-Yu Zhang, master’s degree, now studying in the First Affiliated Hospital of Jinzhou Medical University, focusing on molecular targeted therapy of cancer.
Zheng-Guo Cui
Zheng-Guo Cui, Professor, works in the University Of Fukui School Of Medical Sciences, specializing in environmental science and medical health research.
Li Zhang
Li Zhang, chief physician, graduated from Chengde Medical University and now works in the Department of Oncology of the Affiliated Hospital of Chengde Medical University. He is engaged in the research of radiotherapy, early diagnosis of malignant tumors, and comprehensive treatment of lung cancer, stomach cancer, colorectal cancer, and other tumors, especially the treatment of recurrent refractory tumors with radioactive seed implantation of brachytherapy.
Hua-Chuan Zheng
Hua-Chuan Zheng, chief physician and professor, graduated from China Medical University and now works in Department of Oncology, the First Affiliated Hospital of Jinzhou Medical University. My majors are oncological medicine, molecular mechanisms of carcinogenesis and subsequent progression, spontaneous tumor models of genetically-modified animals and target therapy of cancers.