Wen-Jing Yun, Jun Li, Nan-Chang Yin, Cong-Yu Zhang, Zheng-Guo Cui, Li Zhang, Hua-Chuan Zheng
{"title":"The facilitating effects of KRT80 on chemoresistance, lipogenesis, and invasion of esophageal cancer.","authors":"Wen-Jing Yun, Jun Li, Nan-Chang Yin, Cong-Yu Zhang, Zheng-Guo Cui, Li Zhang, Hua-Chuan Zheng","doi":"10.1080/15384047.2024.2302162","DOIUrl":null,"url":null,"abstract":"<p><p>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 (<i>p</i> < .05), opposite to KRT80 methylation (<i>p</i> < .05). There was a negative relationship between promoter methylation and expression level of KRT80 gene in esophageal cancer (<i>p</i> < .05). KRT80 mRNA expression was positively correlated with the differentiation, infiltration of immune cells, and poor prognosis of esophageal cancer (<i>p</i> < .05). KRT80 mRNA expression was positively linked to no infiltration of immune cells, the short survival time of esophageal cancers (<i>p</i> < .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 (<i>p</i> < .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 (<i>p</i> < .05). KRT80 knockdown suppressed anti-apoptosis, anti-pyroptosis, migration, invasion, chemoresistance, and lipogenesis in esophageal cancer cells (<i>p</i> < .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.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":"25 1","pages":"2302162"},"PeriodicalIF":4.4000,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10802210/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Biology & Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/15384047.2024.2302162","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/19 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
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.
期刊介绍：
Cancer, the second leading cause of death, is a heterogenous group of over 100 diseases. Cancer is characterized by disordered and deregulated cellular and stromal proliferation accompanied by reduced cell death with the ability to survive under stresses of nutrient and growth factor deprivation, hypoxia, and loss of cell-to-cell contacts. At the molecular level, cancer is a genetic disease that develops due to the accumulation of mutations over time in somatic cells. The phenotype includes genomic instability and chromosomal aneuploidy that allows for acceleration of genetic change. Malignant transformation and tumor progression of any cell requires immortalization, loss of checkpoint control, deregulation of growth, and survival. A tremendous amount has been learned about the numerous cellular and molecular genetic changes and the host-tumor interactions that accompany tumor development and progression. It is the goal of the field of Molecular Oncology to use this knowledge to understand cancer pathogenesis and drug action, as well as to develop more effective diagnostic and therapeutic strategies for cancer. This includes preventative strategies as well as approaches to treat metastases. With the availability of the human genome sequence and genomic and proteomic approaches, a wealth of tools and resources are generating even more information. The challenge will be to make biological sense out of the information, to develop appropriate models and hypotheses and to translate information for the clinicians and the benefit of their patients. Cancer Biology & Therapy aims to publish original research on the molecular basis of cancer, including articles with translational relevance to diagnosis or therapy. We will include timely reviews covering the broad scope of the journal. The journal will also publish op-ed pieces and meeting reports of interest. The goal is to foster communication and rapid exchange of information through timely publication of important results using traditional as well as electronic formats. The journal and the outstanding Editorial Board will strive to maintain the highest standards for excellence in all activities to generate a valuable resource.
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