CDC23 regulates cancer cell phenotype and is overexpressed in papillary thyroid cancer

Abstract

Cancer gender disparities have been observed for a variety of human malignancies. Thyroid cancer is one such example where there is a dramatic difference in the incidence, aggressiveness, and death rate by gender. The molecular basis for gender disparity is poorly understood. To address this, we performed genome-wide gene expression profiling in matched papillary thyroid cancer (PTC) samples and identified nine candidate genes differentially expressed by gender. One of these genes was CDC23 that was upregulated in PTC in men compared with women. Because the function and expression of CDC23 is unknown in eukaryotic cells, we further characterized the expression of CDC23 in normal, hyperplastic, and PTC tissue samples. We found CDC23 was overexpressed in PTC and absent in normal and hyperplastic thyroid tissue. In thyroid cancer cells, functional knockdown of CDC23 resulted in an increase in the number of cells in both the S and G 2 M phases of the cell cycle, and an inhibition of cellular proliferation, tumor spheroid formation, and anchorage-independent growth. Cellular arrest in both S and G 2 M phases was associated with significant cyclin B1 and securin protein accumulation after CDC23 knockdown. Moreover, the effect of CDC23 on cellular proliferation and cell cycle progression was reversed on triple knockdown studies of CDC23, cyclin B1, and securin. Our data taken together suggests CDC23 has important biologic effects on cell proliferation and cell cycle progression. The effect of CDC23 on cellular proliferation and cell cycle progression is mediated, at least in part, by cyclin B1 and securin protein levels. Therefore, we propose that CDC23 is a critical regulator of cell cycle and cell growth, and may be involved in thyroid cancer initiation and progression, and may explain the different tumor biology observed by gender.

Gender-Specific Variation in the Prognosis of Papillary Thyroid Cancer TNM Stages II to IV

“…During the processes of tumor initiation and progression, it has been reported that sex hormones may influence the rates of cancer cell proliferation, migration, or apoptotic change [14, 15]. …”

Lower Concentrations of Blueberry Polyphenolic-Rich Extract Differentially Alter HepG2 Cell Proliferation and Expression of Genes Related to Cell-Cycle, Oxidation and Epigenetic Machinery

“…Regulators of cell cycle progression Inhibits cyclin-dependent kinases [41] Cell division cycle 23 homolog (CDC23) A component of anaphase-promoting complex [55] Cyclin D 1 (CCND1) Involves in G1/S cell cycle transition [38,56] Cyclin E 1 (CCNE1) Involves in G1/S cell cycle transition [56] Cyclin B 1 (CCNB1) Involves in regulation of G2/M cell cycle transition [56,57] Proliferating cell nuclear antigen (PCNA) Regulates the processivity of DNA replication in S-phase [58] phase when compared to control ( Figures 4A and table 2). The percent of cells in S-phase was significantly decreased only by the 25 µg/mL concentration, which reduced it by 19% as compared to the control group ( Figures 4C and table 2).…”

Molecular Characterization and Clinical Relevance of m6A Regulators in Metastatic Prostate Cancer

“…RBBP4 could promote the malignant progression of colon cancer through the Wnt/β-catenin pathway [33]. CDC23 regulates the tumour cell phenotype and is upregulated in papillary thyroid cancer [34]. Cell division cycle 5-like (CDC5L) protein, a cell phase regulator of the G2/M transition, has been demonstrated to improve bladder cancer cell proliferation, migration and invasion [35].…”