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CDC6, a key replication licensing factor, is overexpressed and confers poor prognosis in diffuse large B-cell
Mingfang Shen1, Yunfeng Zhang1, Lun Tang1
1Department of Hematology, the First Hospital of Jiaxing, 314001, Zhejiang, China.
BMC Cancer
|October 13, 2023
Summary
Cell division cycle 6 (CDC6) promotes diffuse larger B-cell lymphoma (DLBCL) cell proliferation and survival by regulating the cell cycle and apoptosis. CDC6 is overexpressed in DLBCL and can serve as a novel prognostic marker.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Cell division cycle 6 (CDC6) is a critical licensing factor for DNA replication initiation.
- The specific role of CDC6 in the pathogenesis of diffuse larger B-cell lymphoma (DLBCL) is currently unknown.
- Understanding CDC6's function in DLBCL is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the impact of CDC6 on DLBCL cell proliferation, apoptosis, and cell cycle regulation.
- To elucidate the molecular mechanisms underlying CDC6's effects in DLBCL.
- To correlate CDC6 expression levels with clinical features and patient prognosis in DLBCL.
Main Methods:
- Bioinformatic analysis to identify CDC6's potential role in DLBCL.
- Overexpression and knockdown of CDC6 in DLBCL cell lines (SUDHL4, OCI-LY7) using lentiviral vectors.
- Assessment of cell proliferation (CCK-8), apoptosis (Annexin-V/7-AAD), and cell cycle (flow cytometry).
- Analysis of CDC6 expression and downstream signaling pathways via qRT-PCR and Western blot.
- Immunohistochemical evaluation of CDC6 expression in patient tissues and correlation with clinical data.
Main Results:
- In silico analysis indicated that CDC6 overexpression correlates with poorer DLBCL prognosis.
- CDC6 overexpression enhanced DLBCL cell proliferation, while knockdown inhibited it.
- CDC6 overexpression decreased G1 phase cells; knockdown induced G1 arrest and increased apoptosis.
- CDC6 modulated the expression of cell cycle regulators (INK4, ATR) and apoptosis markers (Bcl-2, Bax).
- CDC6 was overexpressed in DLBCL tissues compared to reactive hyperplasia and associated with non-GCB subtype and unfavorable outcomes (PFS, OS).
Conclusions:
- CDC6 promotes DLBCL cell proliferation and survival by influencing the G1/S cell cycle checkpoint and apoptosis.
- CDC6 is significantly overexpressed in DLBCL.
- CDC6 represents a potential novel prognostic biomarker for DLBCL patients.
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