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CCNB1, Negatively Regulated by miR-559, Promotes the Proliferation, Migration, and Invasion of Ovarian Carcinoma Cells.
- Source :
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Molecular biotechnology [Mol Biotechnol] 2022 Sep; Vol. 64 (9), pp. 958-969. Date of Electronic Publication: 2022 Mar 09. - Publication Year :
- 2022
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Abstract
- Cyclin B1 (CCNB1) is regarded as an oncogene in multiple tumors. This work aims to investigate the expression, function, and related mechanisms of CCNB1 in ovarian carcinoma (OC). Three microarray datasets (GSE14407, GSE18520, and GSE54388) were obtained from the Gene Expression Omnibus (GEO) database and screened for differentially expressed genes (DEGs) of OC tissues and normal ovarian tissues. CCNB1 expression in OC tissues and paracancerous tissues was detected by immunohistochemistry. Kaplan-Meier plotter database was utilized to analyze the correlation between CCNB1 expression and the prognosis of OC patients. After the loss-of-function and gain-of-function cell models were established, cell counting kit-8 (CCK-8), bromo-deoxyuridine (BrdU), and transwell experiments were employed to examine the proliferation, migration, and invasion of OC cells, respectively. The targeting relationship between miR-559 and CCNB1 was verified using the dual-luciferase reporter gene experiment. The expressions of CCNB1 mRNA and miR-559 were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Western blot was used to quantify the protein expression of CCNB1. In addition, xenograft nude mouse models were established to examine the effects of CCNB1 on lung metastasis in vivo. CCNB1 expression was markedly increased in OC tissues and cell lines. The overall survival, progression-free survival, and post-progression survival of OC patients with high CCNB1 expression were significantly shorter. OC cell proliferation, migration, and invasion were enhanced by CCNB1 overexpression while CCNB1 knockdown led to opposite effects. MiR-559 expression was remarkably reduced in OC tissues and cell lines, and miR-559 markedly suppressed the malignant characteristics of OC cells. Besides, miR-559 directly targeted the 3' UTR of CCNB1 mRNA and reduced CCNB1 expression at both the mRNA and protein levels. Overexpression of CCNB1 accelerated lung metastasis of OC cells in vivo. CCNB1, of which expression is modulated by miR-559, facilitates proliferation, migration, and invasion of OC cells, therefore, working as a potential therapeutic target of OC. This work provides new insights into the clinical diagnosis and treatment of OC.<br /> (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
- Subjects :
- 3' Untranslated Regions
Animals
Cell Line, Tumor
Cell Movement genetics
Cell Proliferation genetics
Cyclin B1 genetics
Cyclin B1 metabolism
Female
Gene Expression Regulation, Neoplastic
Humans
Mice
Lung Neoplasms genetics
MicroRNAs genetics
MicroRNAs metabolism
Ovarian Neoplasms genetics
Ovarian Neoplasms metabolism
Ovarian Neoplasms pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1559-0305
- Volume :
- 64
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Molecular biotechnology
- Publication Type :
- Academic Journal
- Accession number :
- 35262876
- Full Text :
- https://doi.org/10.1007/s12033-022-00463-7