Downregulation of the ubiquitin ligase KBTBD8 prevented epithelial ovarian cancer progression

Autor: Yuan Zou, Lei Du, Xiaohua Li, Cong-Rong Li, Linfei Yang, Zhi-Xia Yang, Qi-Feng He, Dong Zhang, Xiao-Wei Xing
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Adult
endocrine system diseases
Somatic cell
Biology
Carcinoma
Ovarian Epithelial
lcsh:Biochemistry
Ovarian tumor
Mice
Downregulation and upregulation
Cell Line
Tumor
Genetics
Biomarkers
Tumor
Animals
Humans
lcsh:QD415-436
Female fertility factor
Molecular Biology
Genetics (clinical)
KBTBD8
Adaptor Proteins
Signal Transducing
Aged
Neoplasm Staging
Ovarian Neoplasms
Gene knockdown
Cell growth
Kinase
lcsh:RM1-950
Middle Aged
Epithelial ovarian cancer
Molecular medicine
Immunohistochemistry
female genital diseases and pregnancy complications
Ubiquitin ligase
Gene Expression Regulation
Neoplastic
Disease Models
Animal
lcsh:Therapeutics. Pharmacology
Tissue Array Analysis
Gene Knockdown Techniques
biology.protein
Cancer research
Disease Progression
Molecular Medicine
Heterografts
Female
Neoplasm Grading
Research Article
Zdroj: Molecular Medicine, Vol 26, Iss 1, Pp 1-16 (2020)
Molecular Medicine
ISSN: 1528-3658
1076-1551
DOI: 10.1186/s10020-020-00226-7
Popis: Objectives Kelch repeat and BTB domain-containing protein 8, KBTBD8, has been identified as a female fertility factor. However, there have been no reports on the role of KBTBD8 in the progression of epithelial ovarian cancer, EOC. Our study aimed to address this issue. Methods We first examine KBTBD8 expression in EOC tissues and cells. Next, we performed RNA sequencing to reveal the overall mechanism. Then we investigated the roles of KBTBD8 in the proliferation, migration, and health status of cultured EOC cells. Finally, we employed tumor xenograft models to evaluate the role of KBTBD8 in vivo. Results First, KBTBD8 level was significantly higher in EOC tissues and cells. Next, comparative RNA sequencing identified more tumorigenesis-related genes that KBTBD8 might regulate. Then we found that KBTBD8 knockdown significantly decreased EOC cell proliferation, migration, and the activities of multiple tumorigenesis-related kinases. Finally, KBTBD8 knockdown significantly diminished ovarian tumor formation in vivo. Conclusion Proper KBTBD8 level is essential for the healthy growth of ovarian somatic cells, such as ovarian epithelial cells. Excessive KBTBD8 might be a significant impetus for EOC progression. KBTBD8 reduction greatly inhibits EOC proliferation and migration.
Databáze: OpenAIRE
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