CDC6 regulates both G2/M transition and metaphase‐to‐anaphase transition during the first meiosis of mouse oocytes

Yi, Zi‐Yun; Meng, Tie‐Gang; Li, Jian; Zhang, Chunhui; Ouyang, Ying‐Chun; Schatten, Heide; Qiao, Jie; Sun, Qing‐Yuan; Qian, Weiping

doi:10.1002/jcp.29469

Cited by 16 publications

(15 citation statements)

References 46 publications

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“…Therefore, CDC6 overexpression may promote the continuous G1/S phase transition, which can cause active proliferation of epithelial cells and even malignant transformation. Some studies have found that CDC6 is also involved in regulating s-G2/M checkpoint, coordinating the process from the S phase to the M phase, and preventing cells from entering the mitotic M phase before the completion of S- phase DNA replication [16,17]. Its expression requires strict regulation to ensure a normal cell cycle [3].…”

Section: Discussionmentioning

confidence: 99%

The Effect of High CDC6 Levels on Predicting Poor Prognosis in Colorectal Cancer

et al. 2022

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Introduction: We investigated the function of cell division cycle 6 (CDC6) on the prognosis in colorectal carcinoma (CRC). Methods: CDC6 protein expression levels in 121 patients with colorectal cancer and adjacent normal mucosa were detected by immunohistochemistry. Results: Compared to adjacent normal tissues, CDC6 mRNA level was overexpressed in CRC tissues. Moreover, CDC6 protein levels were expressed up to 93.39% (113/121) in CRC tissues in the cell nucleus or cytoplasm. However, there were only 5.79% (7/121) in normal mucosal tissues with nuclear expression. CDC6 expression was significantly correlated with TNM stage and tumor metastasis. The 5-year survival rate was lower in the high CDC6 expression group than the low group. After silencing of CDC6 expression in SW620 cells, cell proliferation was slowed, the tumor clones were decreased, and the cell cycle was arrested in G1 phase. In multivariate analysis, increased CDC6 protein expression levels in colon cancer tissues were associated with cancer metastasis, TNM stage, and patient survival time. Conclusion: CDC6 is highly expressed in CRC, and downregulation of CDC6 can slow the growth of CRC cells in vitro. It is also an independent predictor for poor prognosis and may be a useful biomarker for targeted therapy and prognostic evaluation.

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Section: Discussionmentioning

confidence: 99%

The Effect of High CDC6 Levels on Predicting Poor Prognosis in Colorectal Cancer

et al. 2022

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“…By constructing a PPI network, a significant module that had a functional role in DNA replication and cell cycle regulation was identified. From the network, most of the top 10 hub genes identified ( CDK1, CCNA2, CCNB1, PLK1, CDC6 and AURKA ) were also associated with similar cell cycle regulatory functions [ 89 , 114 , 115 , 116 , 117 ]. This further reinforces the fundamental involvement of TTAGPs in cellular division.…”

Section: Discussionmentioning

confidence: 99%

Investigating the Role of Telomere and Telomerase Associated Genes and Proteins in Endometrial Cancer

Bradfield

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Hill

et al. 2020

MPs

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Endometrial cancer (EC) is the commonest gynaecological malignancy. Current prognostic markers are inadequate to accurately predict patient survival, necessitating novel prognostic markers, to improve treatment strategies. Telomerase has a unique role within the endometrium, whilst aberrant telomerase activity is a hallmark of many cancers. The aim of the current in silico study is to investigate the role of telomere and telomerase associated genes and proteins (TTAGPs) in EC to identify potential prognostic markers and therapeutic targets. Analysis of RNA-seq data from The Cancer Genome Atlas identified differentially expressed genes (DEGs) in EC (568 TTAGPs out of 3467) and ascertained DEGs associated with histological subtypes, higher grade endometrioid tumours and late stage EC. Functional analysis demonstrated that DEGs were predominantly involved in cell cycle regulation, while the survival analysis identified 69 DEGs associated with prognosis. The protein-protein interaction network constructed facilitated the identification of hub genes, enriched transcription factor binding sites and drugs that may target the network. Thus, our in silico methods distinguished many critical genes associated with telomere maintenance that were previously unknown to contribute to EC carcinogenesis and prognosis, including NOP56, WFS1, ANAPC4 and TUBB4A. Probing the prognostic and therapeutic utility of these novel TTAGP markers will form an exciting basis for future research.

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“…We found that overexpression of Cdt1 leads to embryos arrest at zygotes stages, but the development with overexpressed MCM2 embryos is not affected, consistent with the expression patterns of Cdt1 and Mcm2 , revealing that CDT1 mainly regulates DNA replication as a regulator, while MCM2 is only involved in DNA replication as an ATPase. CDC6 has been shown to be involved in regulating meiosis in addition to being a subunit of PRC 13 . and CDT1 is involved in regulating kinetochore–microtubule attachments in mitosis 12 .…”

Section: Discussionmentioning

confidence: 99%

CDT1 is the major functional regulatory subunit of the pre‐replication complex in zygotes

Tan

Wang

et al. 2022

Cell Proliferation

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Pre‐replication complex (pre‐RC) is critical for DNA replication initiation. CDT1 and MCM2 are the subunits of pre‐RC, and proper regulation of CDT1 and MCM2 are necessary for DNA replication and cell proliferation. The present study aimed to explore the role of CDT1 and MCM2 in oocyte meiotic maturation and early embryonic development. The depletion and overexpression of Cdt1 and Mcm2 in oocyte and zygote were achieved by microinjecting specific siRNA and mRNA to explored their functions in oocyte meiotic maturation and embryonic development. Then, we examined the effect of CDT1 and MCM2 on other signal pathways by immunostaining the expression of related maker genes. We showed that neither depletion nor overexpression of Cdt1 affected oocyte meiotic progressions. The CDT1 was degraded in S phase and remained at a low level in G2 phase of zygote. Exogenous expression of Cdt1 in G2 phase led to embryo attest at zygote stage. Mechanistically, CDT1 overexpression induced DNA re‐replication and thus DNA damage check‐point activation. Protein abundance of MCM2 was stable throughout the cell cycle, and embryos with overexpressed MCM2 could develop to blastocysts normally. Overexpression or depletion of Mcm2 also had no effect on oocyte meiotic maturation. Our results indicate that pre‐RC subunits CDT1 and MCM2 are not involved in oocyte meiotic maturation. In zygote, CDT1 but not MCM2 is the major regulator of DNA replication in a cell cycle dependent manner. Furthermore, its' degradation is essential for zygotes to prevent from DNA re‐replication in G2 stage.

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CDC6 regulates both G2/M transition and metaphase‐to‐anaphase transition during the first meiosis of mouse oocytes

Cited by 16 publications

References 46 publications

The Effect of High CDC6 Levels on Predicting Poor Prognosis in Colorectal Cancer

The Effect of High CDC6 Levels on Predicting Poor Prognosis in Colorectal Cancer

Investigating the Role of Telomere and Telomerase Associated Genes and Proteins in Endometrial Cancer

CDT1 is the major functional regulatory subunit of the pre‐replication complex in zygotes

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