The international journal of biochemistry & cell biology · 2019
Downregulation of Rab23 inhibits proliferation, invasion, and metastasis of human ovarian cancer.
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Gao Lingling, Zheng Mingjun, Guo Qian, Nie Xin, Li Xiao, Hao Yingying, Liu Juanjuan, Zhu Liancheng, Lin Bei
Аннотация
Previously, we reported that the expression of human epididymis protein (HE4) was correlated with the expression of RAB23 in ovarian cancer cells. Rab23 is a member of the Ras-related small GTPase superfamily, which plays a key role in the Sonic Hedgehog (Shh) signaling pathway. However, the function of Rab23 in ovarian cancer remains unclear. In this study, we explored the location and expression of Rab23 in ovarian cancer tissues and cells (CaoV3 and A2780), and further investigated the function and potential mechanism of Rab23 in malignant biological behaviors including the epithelial-mesenchymal transition (EMT) process in ovarian cancer for the first time. Rab23 is highly expressed in ovarian cancer tissues and associated with advanced stage, and shortened overall survival time of ovarian cancer patients. We are the first to report that human epididymis protein (HE4) can regulate the expression of the Rab23 protein, and that knockdown of RAB23 decreases the proliferation, invasion, and migration abilities as well as inhibits the epithelial-mesenchymal transition (EMT) process in ovarian cancer cells. Furthermore, downregulation of Rab23 significantly inhibited Shh-Gli1 and PI3K-AKT signaling pathways. Collectively, our results indicate that Rab23 plays a critical role in the malignant biological behavior of ovarian cancer and may serve as a potential biomarker and therapeutic target for ovarian cancer.
Предметные рубрики MeSH
AdenocarcinomaAdultAgedAged, 80 and overCase-Control StudiesCell Line, TumorCell MovementCell ProliferationEpithelial-Mesenchymal TransitionFemaleGene Expression Regulation, NeoplasticHedgehog ProteinsHumansMiddle AgedNeoplasm StagingNeoplasmsOvarian NeoplasmsPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktRNA, Small InterferingSignal TransductionSurvival AnalysisWAP Four-Disulfide Core Domain Protein 2Zinc Finger Protein GLI1rab GTP-Binding Proteins