Abstract
ObjectivesKelch 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.MethodsWe 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.ResultsFirst, 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.ConclusionProper 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.
Highlights
Ovarian cancer is one of the most common malignant tumors of the female organs
Human Kelch repeat and BTB domain-containing protein 8 (KBTBD8) was overexpressed in multiple clinical ovarian cancer samples a total of 13 Kelch repeat and BTB domain-containing (KBTBD) family members are currently known, none have been reported to be involved in Epithelial ovarian cancer (EOC) progression
In a previous transcriptome-wide screen of genes required for follicle maturation and development, KBTBD8 was the only member of the KBTBD gene family that was identified as a female fertility factor (Gallardo et al 2007)
Summary
Ovarian cancer is one of the most common malignant tumors of the female organs. the incidence of ovarian malignancy, mostly epithelial ovarian cancer (EOC), ranks third overall, the mortality rate in EOC patients is the highest among all types of gynecologic tumors (Bray et al 2018; Smith et al 2018; TorreThe mechanism(s) governing ovary tumorigenesis is complex. Ovarian cancer is one of the most common malignant tumors of the female organs. The incidence of ovarian malignancy, mostly epithelial ovarian cancer (EOC), ranks third overall, the mortality rate in EOC patients is the highest among all types of gynecologic tumors Ubiquitination is an important type of protein post-translational modification that labels a target protein with mono- or polyubiquitin. Ubiquitination usually conduces to protein degradation by the proteosome complex. In this case, if ubiquitination is inhibited, the target protein will become hyperactivated; the chance of tumorigenesis will increase. The Notch signaling pathway is critically involved in breast and ovarian cancers, while the E3 ubiquitin protein ligase
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