Abstract
The pattern of VPS9D1-AS1 expression and its effects on uterine corpus endometrial carcinoma (UCEC) remained unclear. VPS9D1-AS1, miR-520a-5p, and BIRC5 mRNA levels were quantified by qRT-PCR. Bax, Bcl-2, N-cadherin, E-cadherin, and BIRC5 protein levels were analyzed through western blotting. Cell migration, invasion, proliferation, as well as apoptosis of cells were checked after performing assay for wound-healing, Transwell, cell-counting kit-8 (CCK-8) assay, and western blotting. VPS9D1-AS1 effects on UCEC were observed in nude mice. Through bioinformatics tools, we analyzed the association present among miR-520a-5p, BIRC5, and VPS9D1-AS1 along with RNA immunoprecipitation, and Dual-Luciferase verification reporter analysis. Our findings suggested VPS9D1-AS1 gene expression was up-regulated in both tissues as well as cells of UCEC. VPS9D1-AS1 knockdown suppressed migration, invasion, epithelial-mesenchymal transition (EMT) along with proliferation of UCEC cells, caused in vitro cell apoptosis initiation, and in vivo reduction of tumor growth. Mechanistically, it was verified that VPS9D1-AS1 targeted BIRC5 and caused miR-520a-5p sponging. Inhibitor of miR-520-5p markedly reversed the anti-tumor effects of VPS9D1-AS1 knockdown or BIRC5 knockdown on UCEC progression. Our studies revealed that VPS9D1-AS1 contributed to the UCEC development and progression by binding to miR-520a-5p competitively and inducing BIRC5 expression, indicating that VPS9D1-AS1 might act as a therapeutic target to develop new therapies for UCEC patients.
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The datasets used in the current study and/or analyzed during the study are available on request from the corresponding author.
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LC: conducted all experiments and analyzed the data. MS: designed and planned the current study. MS: made the attainment of data. LC: analyzed and interpreted the data. The manuscript was approved by all authors.
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Ethics Committee of The Sixth Hospital of Wuhan, Affiliated Hospital of Jianghan University (Wuhan, China) approved the current study. All experiments conducted on tissue samples are in strict compliance with the Declaration of Helsinki’s ethical standards. Patients have signed the given informed consent before their participation. This animal experiment was conducted in accordance with the ARRIVE guidelines and was authorized by the Ethics Committee of The Sixth Hospital of Wuhan, Affiliated Hospital of Jianghan University.
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Chen, L., Shen, M. LncRNA VPS9D1-AS1 Sponging miR-520a-5p Contributes to the Development of Uterine Corpus Endometrial Carcinoma by Enhancing BIRC5 Expression. Mol Biotechnol 64, 1328–1339 (2022). https://doi.org/10.1007/s12033-022-00510-3
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DOI: https://doi.org/10.1007/s12033-022-00510-3