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miR-30c-2-3p suppresses the proliferation of human renal cell carcinoma cells by targeting TOP2A

BACKGROUND: The ambiguity of renal cell carcinoma (RCC) symptoms hinders early diagnosis, thereby contributing to high mortality rates. By attaching to the 3′-untranslated region (UTR) of the target gene, microRNAs (miRNAs) exert significant control over the expression of genes. OBJECTIVES: To inves...

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Detalles Bibliográficos
Autores principales: Huang, Xiaoyong, Jia, Yuna, Shi, Haiyan, Fan, Haiyan, Sun, Lingbo, Zhang, Huahua, Wang, Yanfeng, Chen, Jie, Han, Jiaqi, Wang, Mingming, Du, Juan, Zhang, Jing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Sciendo 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10561683/
https://www.ncbi.nlm.nih.gov/pubmed/37818158
http://dx.doi.org/10.2478/abm-2023-0052
Descripción
Sumario:BACKGROUND: The ambiguity of renal cell carcinoma (RCC) symptoms hinders early diagnosis, thereby contributing to high mortality rates. By attaching to the 3′-untranslated region (UTR) of the target gene, microRNAs (miRNAs) exert significant control over the expression of genes. OBJECTIVES: To investigate the influence of miR-30c-2-3p and DNA topoisomerase II alpha (TOP2A) on RCC growth and the mechanisms underlying the regulation of its expression. METHODS: The expression of miRNA-30c-2-3p and TOP2A in RCC cells was examined using quantitative real-time polymerase chain reaction (qRT-PCR). MiR-30c-2-3p mimics, its inhibitors, and controls, as well as TOP2A short hairpin RNA (shRNA) and controls, were used to transfect the human RCC cell lines 786-O, Caki-1, and ACHN. Additionally, the roles of miRNA-30c-2-3p and TOP2A in the growth of RCC were evaluated using the cell counting kit (CCK)-8 test, colony formation assay, apoptosis analysis, and Western blotting. Meanwhile, binding of miRNA-30c-2-3p and TOP2A was verified using dual-luciferase reporter assays and Western blotting. RESULTS: miR-30c-2-p is underexpressed in RCC cells. Overexpression of miR-30c-2-p promotes apoptosis and inhibits proliferation of ACHN, Caki-1, and 786-O cells. miR-30c-2-3p targets TOP2A, which is elevated in RCC tissues and cells, whereas TOP2A silencing inhibits the proliferation ability of RCC cells. The miRNA-30c-2-3p inhibitor compromises TOP2A shRNA-induced apoptosis of RCC. RCC cells cotransfected with miRNA-30c-2-3p inhibitors and TOP2A shRNAs have a higher proliferation rate than those transfected with only TOP2A shRNAs. CONCLUSIONS: Collectively, our results verify that miRNA-30c-2-3p has a tumor suppressor property. miRNA-30c-2-3p inhibits the proliferation of RCC through regulation of TOP2A. The data provide a viable therapeutic target for RCC.