Endometrial cancer (EC) is a kind of gynecologic malignancy with a rising incidence rate. This study aimed to explore the role of VPS9D1 antisense RNA1 (VPS9D1-AS1) in EC. The expression of VPS9D1-AS1, microRNA (miR)-377-3p, and serum and glucocorticoid-regulated kinase 1 (SGK1) was detected by Quantitative Real-Time PCR (qRT-PCR). Cell proliferation, invasion and epithelial-mesenchymal transition (EMT) were determined by cell counting kit-8 (CCK-8), 5-Ethynyl-2'-Deoxyuridine (EdU) transwell, and western bolt. VPS9D1-AS1 was predicted to sponge miR-377-3p via Starbase, and verified by luciferase reporter, RNA binding protein immunoprecipitation (RIP), and RNA pull-down experiments. The clinical characteristics of VPS9D1-AS1, miR-377-3p, and SGK1 were analyzed. The role of VPS9D1-AS1 on EC tumorigenesis was assessed in xenografted nude mice. VPS9D1-AS1 was upregulated in EC cells and tissues. Interference of VPS9D1-AS1 inhibited growth, invasion, and EMT of EC cells. Mechanically, VPS9D1-AS1 was a molecular sponge of miR-377-3p, and overexpression of miR-377-3p reversed VPS9D1-AS1-induced EC cells proliferation, invasion, and EMT. Moreover, SGK1 was confirmed to bind with miR-377-3p. Furthermore, overexpression of SGK1 alleviated sh-VPS9D1-AS1-caused effects on EC cells. High level of VPS9D1-AS1 and SGK1, or low miR-377-3p expression predicted a poor prognosis. The expression of the three genes was correlated with lymph node metastasis, pathological stage, and International Federation of Gynecology and Obstetrics (FIGO) stage, but not associated with age, ER, and PR expression. Interestingly, knockdown of VPS9D1-AS1 suppressed EC tumor growth in mice. VPS9D1-AS1 promoted cell invasion, proliferation, and EMT via modulating miR-377-3p/SGK1 axis, which provided new options for therapeutic strategies of EC.
Keywords: SGK1; VPS9D1-AS1; endometrial cancer; miR-377-3p.
© 2022 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.