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CDCA7 Promotes Neuroblastoma Proliferation via Regulating the Cell Cycle
Wen Yuan1, Xiaoxing Huang2, Renwei Luo3
1Department of Laboratory Medicine, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430016, China.
Background:
Cell division cycle-associated 7 (CDCA7) is overexpressed in several malignant cancers and promotes tumorigenesis. However, the clinical and biological functions of CDCA7 in neuroblastoma (NB) are unclear.
Objectives:
This study aimed to investigate the expression pattern, clinical significance, and biological functions of CDCA7 in neuroblastoma, and to elucidate its potential molecular mechanisms in regulating cell proliferation and cell cycle progression.
Materials And Methods:
The NB database was used to evaluate the predictive significance of CDCA7 and its correlation with clinical features of NB. The prognostic significance of mRNA expression of CDCA7 in lung cancer was evaluated using Kaplan-Meier Analysis. Stable knockdown of CDCA7 was achieved using shRNA and cell proliferation was evaluated using the CCK8 assay. Flow cytometry was used to analyze the cell cycle distribution. The effects of CDCA7 interference on cell cycle-related proteins in NB cells were measured by fluorescence quantitative PCR and Western blotting. Additionally, the role of CDCA7 in human immunity was examined.
Results:
In this study, we screened NB datasets and found that CDCA7 was highly expressed in NB tissues and cell lines compared with normal tissues and cell lines. CDCA7 expression was notably higher in MYCN-amplified NB tissues than that in their non-MYCN-amplified counterparts. Furthermore, increased CDCA7 expression was significantly associated with advanced tumor stages. Additionally, high CDCA7 expression may predict poor overall survival (OS) and event-free survival (EFS) in patients with NB. Moreover, Silencing CDCA7 effectively reduced cell proliferation, increased the proportion of cells in G1 phase, and lowered cyclin-dependent kinase 6 (CDK6) expression. CDCA7 is closely associated with immune cell infiltration by B cells, CD4+ T cells, and macrophages.
Conclusion:
CDCA7 may serve as a prognostic marker for neuroblastoma. Its silencing leads to G1 cell cycle arrest and a reduction in CDK6 expression, ultimately inhibiting NB cell proliferation.
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