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KMID : 0381120220440111375
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Genes and Genomics
2022 Volume.44 No. 11 p.1375 ~ p.1384
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Rab11a promotes the malignant progression of ovarian cancer by inducing autophagy
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Wang Yazhuo
Ren Yanan
Li Na
Zhao Jing
Zhao Sufen
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Abstract
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Background: Rab11a is a novel identified tumorigenic factor involved in different cancers.
Objective: This study aimed to assess the biological function of Rab11a in ovarian cancer (OC).
Methods: GEPIA database and real-time PCR were used to determine Rab11a expression in OC tissues and normal ovarian tissues. CCK-8, cell cycle, wound healing, transwell, and enzyme linked immunosorbent assay were used to detect the effects of Rab11a knockdown or overexpression on the proliferation, migration, and invasion of OC cells. Western blot analysis of autophagy-related markers and immunofluorescence staining of LC3 were performed to determine autophagy induction in Rab11a-silenced or overexpressed OC cells. Moreover, autophagy inhibitor 3-MA was employed to clarify the effects of Rab11a-regulated autophagy on the malignant phenotypes of OC cells.
Results: The mRNA level of Rab11a was increased in tumor tissues from OC patients as compared to the normal ovarian tissues. Knockdown of Rab11a in OVCAR-3 cells inhibited the growth of OC cells and led to cell cycle arrest, accompanied by reduced expression of PCNA and Cyclin D1. Rab11a deficiency suppressed migration and invasion of OC cells, accompanied by decreased secretion of MMP-2 and MMP-9. Silence of Rab11a impeded autophagy induction, as evidenced by decreased LC3 puncta formation, reduced abundance of LC3II and Beclin1, and increased p62 protein expression. In contrast, the ectopic expression of Rab11a in A2780 cells exerted opposite effects. Interestingly, autophagy inhibitor 3-MA abolished the effects of Rab11a overexpression on autophagy, proliferation, migration, and invasion.
Conclusions: Rab11a promotes the malignant phenotypes of OC cells by inducing autophagy.
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KEYWORD
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Rab11a, Ovarian cancer, Malignant phenotypes, Autophagy
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