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Role of POLE2/GINS1-mediated AKT/mTOR pathway in RCC autophagy, proliferation, and metastasis: evidences from
Yajuan Su1, Wentao Wang2, Xingyuan Wang2
1Department of Clinical Laboratory, Harbin Medical University Cancer Hospital, Harbin, 150081, China.
Abstract:
POLE2 exhibits oncogenic properties. This study aimed to clarify its effects and underlying mechanisms in renal cell carcinoma (RCC). Using bioinformatics analyses, we predicted the relationship between POLE2 and autophagy, epithelial-mesenchymal transformation (EMT), and the AKT/mTOR pathway. The expression pattern of POLE2 was further verified in the clinical cohort comprising 94 tumor samples from patients with RCC. Following, we constructed in vivo and in vitro models to further investigate the potential mechanisms of POLE2 using a series of molecular biology approaches. The results showed that GINS1 was the downstream target of POLE2, and its overexpression reversed the inhibitory effects of POLE2 knockdown on RCC proliferation, metastasis, and EMT, while restoring the autophagy suppression. Furthermore, POLE2/GINS1 inhibited AKT/mTOR-mediated autophagy, thereby promoting EMT and lung metastasis of RCC. These findings provide a more comprehensive perspective on the genetic function of POLE2 in RCC progression.
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