Cell Division Cycle Associated 5 Expression Research Articles

CDCA5 promoted cell invasion and migration by activating TGF-β1 pathway in human ovarian cancer cells

BackgroundThe gene cell division cycle associated 5 (CDCA5), also called sororin, has oncogenic characteristics and is upregulated in various carcinomas. Nevertheless, the involvement of CDCA5 in ovarian cancer (OC), a highly aggressive form of cancer, and the underlying mechanism of metastasis remain inadequately investigated.ResultsThe bioinformatics data revealed a negative correlation between the patient’s survival and CDCA5 expression, which was overexpressed in OC. Functional assays also confirmed high expression levels of CDCA5 in OC tissues and cells. This suggests that CDCA5 may potentially enhance the motility, migration, and proliferation of OC cells invitro. It impedes DNA damage and apoptosis in OC cells, inhibiting xenograft development in nude mice. The RNA sequencing results suggest CDCA5 is majorly associated with biological functions related to the extracellular matrix (ECM) and influences the transforming growth factor (TGF) signaling pathway. Moreover, subsequent functional investigations elucidated that CDCA5 facilitated the migration and invasion of OC cells viathe TGF-β1/Smad2/3 signaling pathway activation.ConclusionsCDCA5 may be a strong potential therapeutic target for the treatment and management of OC.

An integrated model of CDCA5 and FOXM1 expression combined with a residual disease that predicts prognosis in ovarian cancer patients.

Ovarian cancer (OC) is the most prevalent type of gynecologic cancer, leading to global death. Unfortunately, less than half of patients diagnosed with this cancer survive for up to five years. The factor forkhead box M1 (FOXM1) is a crucial oncoprotein in ovarian cancer and is currently recognized as a potential therapeutic target. The role of the Cell division cycle-associated 5 (CDCA5) is critical for advancing different types of cancers. However, the significance of CDCA5 in OC from a clinical perspective is not well comprehended. This study aimed to build a risk prognosis model and assess the data supporting the prognostic usefulness of CDCA5 and FOXM1 expression in patients with OC. In OC, we found that CDCA5 and FOXM1 were expressed. To establish the existence of variables that were independently related to PFS and OS, Cox regression, data from clinics, and Kaplan-Meier analysis were used. A risk score model and nomogram were created using the independent prognostic parameters. The accuracy of the model's predictions was then evaluated using decision curve analysis (DCA), calibration curve, and receiver operating characteristic(ROC) analysis. Finally, the patients were separated into groups based on their cut-off value, and then the differences in survival were investigated. Significant correlations were found between OC and CDCA5, and FOXM1 expression levels (P <0.0001). Serous ovarian tumors (P=0.025) and even specific subgroups of high-grade serous ovarian tumors were shown to have elevated CDCA5 expression levels. In our database, FOXM1 expression levels were discovered to be related to intestinal metastases (P=0.014). In OC, the expression of FOXM1 was positively correlated with the overexpression of CDCA5 (rs=0.46, P<0.0001). The results of the multivariate analysis indicated that residual disease (RD) (P=0.005), CDCA5 expression level (P=0.028), and FOXM1 expression level (P<0.0001) were identified as independent prognostic factors for PFS. Additionally, RD (P=0.023) and FOXM1 expression level (P<0.0001) were identified as independent prognostic factors for OS. While the prediction model's performance with RD was poor (AUC=0.645 for PFS, AUC=0.650 for OS), the model's performance with tissue biomarkers was enhanced (AUC=0.797 for PFS, AUC=0.741 for OS). The nomogram and risk score method showed a benefit for prognosis prediction. In summary, poor outcomes are predicted by CDCA5, which is overexpressed in OC patients and has a positive correlation with the level of FOXM1 expression. An aid to prognosis prediction in patients with OC and a resource for therapy planning is a risk prognosis model based on CDCA5 and FOXM1 expression with RD.

The Comprehensive Analysis Illustrates the Role of CDCA5 in Breast Cancer: An Effective Diagnosis and Prognosis Biomarker.

Several studies have been conducted to investigate the role of cell division cycle-associated 5 (CDCA5) in cancer. Its role in breast cancer, however, remains unknown. The Gene Expression Omnibus and Cancer Genome Atlas Program databases provided the open-access information needed for the research. The CCK8 and colony formation assays were used to measure cell proliferation. The capacity of breast cancer cells to invade and migrate was assessed using the transwell assay. In our study, CDCA5 was identified as the interested gene through a series of bioinformatics analysis. We found a higher CDCA5 expression level in tissue and cells of breast cancer. Meanwhile, CDCA5 has been linked to increased proliferation, invasion, and migration of breast cancer cells, which was also associated with worse clinical features. The biochemical pathways, in which CDCA5 was engaged, were identified using biological enrichment analysis. Immune infiltration research revealed that CDCA5 was linked to enhanced activity of several immune function terms. Meanwhile, DNA methylation might be responsible for the aberrant level of CDCA5 in tumor tissue. In addition, CDCA5 could significantly increase the paclitaxel and docetaxel sensitivity, indicating that it has the potential for clinical application. Also, we found that CDCA5 is mainly localized in cell nucleoplasm. Moreover, in the breast cancer microenvironment, we found that CDCA5 is mainly expressed in malignant cells, proliferation T cells, and neutrophils. Overall, our findings suggest that CDCA5 is a potential prognostic indicator and target for breast cancer, which can indicate the direction of the relevant research.

KLF5-mediated CDCA5 expression promotes tumor development and progression of epithelial ovarian carcinoma

Cell division cycle associated 5 (CDCA5) is correlated with the development and progression of many malignant tumors. However, little is known about its role in epithelial ovarian cancer (EOC) progression. In this study, the clinical value, biological function and underlying mechanisms of CDCA5 in EOC were evaluated. CDCA5 mRNA and protein levels were substantially upregulated in EOC and had a significant positive correlation with adverse clinicopathological characteristics and a poor prognosis. CDCA5 facilitated proliferation, invasion, and metastasis and disrupted mitochondrial-mediated endogenous apoptosis by activating the cell cycle pathway and inhibiting the P53 pathway in EOC cells. Conversely, knockdown of CDCA5 expression blocked the malignant activities of EOC cells and suppressed the growth of xenograft tumors in vivo. Mechanistically, the transcription factor KLF5 bound to a specific site in the CDCA5 promoter and promoted CDCA5 expression. Moreover, KLF5 overexpression rescued the negative regulation of inhibited CDCA5 expression on EOC cell proliferation. In conclusion, our findings revealed that CDCA5 promoted tumor progression of EOC via the KLF5/CDCA5/cell cycle and P53 axes, which might provide new insights into the roles of CDCA5 in EOC.

A 1-kb human CDCA8 promoter directs the spermatogonia-specific luciferase expression in adult testis

Cell division cycle associated 8 (CDCA8) is a component of the chromosomal passenger complex and plays an essential role in mitosis, meiosis, cancer growth, and undifferentiated state of embryonic stem cells. However, its expression and role in adult tissues remain largely uncharacterized. Here, we studied the CDCA8 transcription in adult tissues by generating a transgenic mouse model, in which the luciferase was driven by a 1-kb human CDCA8 promoter. Our previous study showed that this 1-kb promoter was active enough to dictate reporter expression faithfully reflecting endogenous CDCA8 expression. Two founder mice carrying the transgene were identified. In vivo imaging and luciferase assays in tissue lysates revealed that CDCA8 promoter was highly activated and drove robust luciferase expression in testes. Subsequently, immunohistochemical and immunofluorescent staining showed that in adult transgenic testes, the expression of luciferase was restricted to a subset of spermatogonia that were located along the basement membrane and positive for the expression of GFRA1, a consensus marker for early undifferentiated spermatogonia. These findings for the first time indicate that the CDCA8 was transcriptionally activated in testis and thus may play a role in adult spermatogenesis. Moreover, the 1-kb CDCA8 promoter could be used for spermatogonia-specific gene expression in vivo and the transgenic lines constructed here could also be used for recovery of spermatogonia from adult testes.

Cell division cycle-associated 8 is a prognostic biomarker related to immune invasion in hepatocellular carcinoma.

Cell division cycle-associated 8 (CDCA8) is involved in numerous signaling networks, and it serves a crucial modulatory function in multiple malignant tumors. However, its significance in prognosis and immune infiltration in hepatocellular carcinoma (HCC) remains unclear. Herein, we examined the CDCA8 levels in tumor tissues, as well as its associated signaling pathways and correlation with immune infiltration. Additionally, we further clarified the prognostic significance of CDCA8 among HCC patients. HCC patient information was recruited from The Cancer Genome Atlas (TCGA). Using bioinformatics, the following parameters were analyzed among HCC patients: CDCA8 expression, enrichment analysis, immune infiltration, and prognosis analysis. Moreover, we employed in vitro investigations, such as, qRT-PCR, immunohistochemistry (IHC), and cell functional experiments to validate our results. Elevated CDCA8 expression in HCC patients was markedly associated with T stage, pathological status (PS), tumor status (TS), histologic grade (HG), and AFP. Elevated CDCA8 expression HCC patients exhibited reduced overall survival (OS) (p < 0.001), disease-specific survival (DSS) (p < 0.001), and progress free interval (PFI) H(p < 0.001). According to the ROC analysis, the area under the curve (AUC) was 0.997. Multivariate analysis revealed that CDCA8 was a stand-alone prognostic indicator of patient OS (p=0.009) and DSS (p=0.006). A nomogram was then generated based on the multivariate analysis, and the C-indexes and calibration chart revealed excellent predictive performance in determining HCC patient outcome. Based on the GSEA analysis, CDCA8 modulated the P53, Notch, PPAR, E2F networks. We observed a direct link between CDCA8 levels and Th2 and T helper cells, and a negative link between CDCA8 levels and dendritic cells (DC), neutrophils, cytotoxic cells, and CD8 T cells. Furthermore, CDCA8 deficiency inhibited liver cancer cell proliferation and invasion. In conclusion, these findings indicate that CDCA8 is a new molecular bioindicator of HCC patient prognosis, and it is an excellent candidate for therapeutic target against HCC.

Mechanistic and Clinical Evidence Supports a Key Role for Cell Division Cycle Associated 5 (CDCA5) as an Independent Predictor of Outcome in Invasive Breast Cancer.

Cell Division Cycle Associated 5 (CDCA5) plays a role in the phosphoinositide 3-kinase (PI3K)/AKT/mTOR signalling pathway involving cell division, cancer cell migration and apoptosis. This study aims to assess the prognostic and biological value of CDCA5 in breast cancer (BC). The biological and prognostic value of CDCA5 were evaluated at mRNA (n = 5109) and protein levels (n = 614) utilizing multiple well-characterized early stage BC cohorts. The effects of CDCA5 knockdown (KD) on multiple oncogenic assays were assessed in vitro using a panel of BC cell lines. this study examined cohorts showed that high CDCA5 expression was correlated with features characteristic of aggressive behavior and poor prognosis, including the presence of high grade, large tumor size, lymphovascular invasion (LVI), hormone receptor negativity and HER2 positivity. High CDCA5 expression, at both mRNA and protein levels, was associated with shorter BC-specific survival independent of other variables (p = 0.034, Hazard ratio (HR) = 1.6, 95% CI; 1.1-2.3). In line with the clinical data, in vitro models indicated that CDCA5 depletion results in a marked decrease in BC cell invasion and migration abilities and a significant accumulation of the BC cells in the G2/M-phase. These results provide evidence that CDCA5 plays an important role in BC development and metastasis and could be used as a potential biomarker to predict disease progression in BC.

Prognostic and Immunological Roles of Cell Cycle Regulator CDCA5 in Human Solid Tumors.

There have been several studies evaluating the prognostic significance of cell division cycle associated 5 (CDCA5). However, few reports analyzed the correlation between CDCA5 and prognosis of diverse cancers based on large clinical data. We thus comprehensively analyzed CDCA5 expression and clinical significance using The Cancer Genome Atlas (TCGA) data from 31 types of solid tumors. The expression profiles of CDCA5 were investigated across pan-cancer samples from the TCGA. Cox regression and Kaplan-Meier analysis was performed to determine CDCA5's prognostic value. CDCA5 expression was further validated by quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC) in lung adenocarcinoma (LUAD). We found that CDCA5 was significantly overexpressed in 22 types of tumors. Up-regulated CDCA5 was significantly related to poor survival in 13 types of tumors. Furthermore, CDCA5 expression was significantly associated with immune cell infiltration. Tumor mutation burden (TMB), microsatellite instability (MSI), and immune checkpoint expression were significantly correlated with CDCA5 expression. Additional analysis of IMvigor 210 cohort validated that patients with high level of CDCA5 had superior response to anti-PD-L1 therapy. Our findings suggested that CDCA5 could provide prognostic information in most types of cancers and contributed to tumor immune microenvironment.

CDCA5 promotes the progression of breast cancer and serves as a potential prognostic biomarker.

Cell division cycle-associated 5 (CDCA5) plays a critical role in the progression of various human cancers by regulating cell cycle-related proteins; however, the function of CDCA5 in breast cancer (BC) is poorly understood. The aim of the present study was to investigate the expression level of CDCA5 in BC and its effect on BC progression. CDCA5 was found to be highly expressed in patients with BC, as well as in BC cell lines. It was also found that a high CDCA5 expression in BC was significantly associated with a shorter survival rate. In addition, the expression level of CDCA5 was significantly increased in stem cells derived from suspension-cultured BC cells, as compared to adherent-cultured cells. CDCA5 knockdown in MCF7 and SKBR3 cells significantly reduced cell proliferation, migration and clone formation. At the same time, the stemness capacity of BC cells, determined by analyzing cancer stem cell marker expression and mammosphere formation, was also markedly diminished following the knockdown of CDCA5. In addition, in vivo experiments demonstrated that CDCA5 knockdown in MCF7 cells markedly reduced tumor growth. On the whole, the present study demonstrates that CDCA5 may be used as a prognostic biomarker and therapeutic target for BC.

LncRNA MIR4435-2HG Accelerates the Development of Bladder Cancer through Enhancing IQGAP3 and CDCA5 Expression.

Background Bladder cancer (BCa) is one of the most prevalent cancers occurring in the urinary system. Long noncoding RNAs (lncRNAs), in recent years, have emerged as crucial regulators in various biological processes of tumors. Aim To identify the role of MIR4435-2 host gene (MIR4435-2HG) and uncover its molecular mechanism in BCa. Methods Firstly, quantitative real-time PCR (RT-qPCR) analysis was used to examine MIR4435-2HG expression in BCa cells. Cell Counting Kit-8 (CCK-8), 5-ethynyl-2′-deoxyuridine (EdU), wound healing, and transwell assays were implemented to identify the role of MIR4435-2HG in BCa. RNA-binding protein immunoprecipitation (RIP), RNA pull down, and luciferase reporter assays were applied to explore the potential mechanism of MIR4435-2HG in BCa. Results MIR4435-2HG was highly expressed in BCa. Moreover, MIR4435-2HG silencing abrogated BCa cell proliferation, migration, and invasion. In terms of underlying mechanism, MIR44352HG acted as a microRNA-2467-3p (miR-2467-3p) sponge to control the expression of IQ motif containing GTPase activating protein 3 (IQGAP3) and cell division cycle associated 5 (CDCA5), resulting in activation of the rat sarcoma virus (Ras)/rapidly accelerated fibrosarcoma (Raf)/mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) and PI3K/AKT/mTOR signaling pathways. Conclusion MIR4435-2HG involves in the progression of BCa, which might provide novel insights for BCa treatment.

Effect of CDCA5 on Proliferation and Metastasis of Triple Negative Breast Cancer Cells under shRNA Interference Technology.

Objective It was to explore the effect of cell division cycle associated 5 (CDCA5) under shRNA interference on proliferation and metastasis of triple negative breast cancer (TNBC) cells. Methods MDA-ME-231 and BT549 cells were selected as the research objects. According to the different interference methods and CDCA5 interference sequences, they were divided into the interference group 1MDA-ME-231, the interference group 2MDA-ME-231, the interference group 1BT549, the interference group 2BT549 (using shRNA technology), the control group MDA-ME-231, and the control group BT549 (breast cancer cells under normal culture conditions). MCF10A cells were routinely cultured as the negative control group to analyze the effect of CDCA5 expression on the proliferation and migration of cancer cells. Results The expression of CDCA5 protein in MDA-ME-231 and BT549 cells in control group was significantly higher than that in negative control group (P < 0.05). Compared with the control group, the inhibition rates of CDCA5 expression in 1MDA-ME-231, 2MDA-ME-231, 1BT549, and 2BT549 cells in the interference group were 39.01%, 42.98%, 49.57%, and 60.98%, respectively (P < 0.05). From 12 h, the proliferation level of TNBC cells at different culture time was lower than that of the control group (P < 0.05). Compared with the number of staining cells in the control group, the positive staining cells in 1MDA-ME-231 (61.42%), 2MDA-ME-231 (72.06%), 1BT549 (52.53%), and 2BT549 (59.65%) in the interference group were significantly decreased (P < 0.05). Conclusion The results show that the expression of CDCA5 in TNBC is increased, which plays an important role in the proliferation and migration of cancer cells. shRNA interference technology can knock down the expression of CDCA5 and inhibit its “promoting cancer” effect.

Loss of cell division cycle‑associated 5 promotes cell apoptosis by activating DNA damage response in clear cell renal cell carcinoma.

Cell division cycle-associated 5 (CDCA5) protein, which is involved in cohesion, contributes to cell cycle regulation and chromosome segregation by maintaining genomic stability. Accumulating evidence indicates that CDCA5 expression is upregulated in a number of types of cancer associated with a poor prognosis. However, the biological function of CDCA5 in clear cell renal cell carcinoma (ccRCC) remains largely unknown. In the present study, The Cancer Genome Atlas data mining revealed that CDCA5 was more highly expressed in ccRCC than in adjacent normal tissues. Importantly, such a high expression was associated with a higher risk of distant metastasis and poorer clinical outcomes. Moreover, the clinical and prognostic value of CDCA5 expression was further investigated using immunohistochemistry on tissue microarrays containing paired tumor tissues and adjacent normal tissues from 137 patients with ccRCC. Functional analyses revealed that CDCA5 knockdown significantly inhibited the proliferation and migration of ccRCC cells, and suppressed the growth of xenografts in nude mice. Mechanistically, CDCA5 knockdown induced severe DNA damage with the persistent accumulation of γ-H2A histone family member X foci, resulting in G2/M cell cycle arrest and finally, in chromosomal instability and apoptosis. CDCA5 knockdown significantly decreased the phosphorylation levels of Stat3 and NF-κB, suggesting that CDCA5 plays a role in regulating the inflammatory response. Collectively, the findings of the present study indicate that ccRCC cells require CDCA5 for malignant progression, and that CDCA5 inhibition may enhance the outcomes of patients with high-risk ccRCC.

Silencing oncogene cell division cycle associated 5 induces apoptosis and G1 phase arrest of non-small cell lung cancer cells via p53-p21 signaling pathway.

BackgroundsAs a regulator of cell cycle, cell division cycle‐associated 5 (CDCA5) is involved in the progression of various malignant tumors. However, the potential relationship between CDCA5 and lung cancer has not been reported.MethodsIn our study, we analyzed the expression of CDCA5 in a variety of malignant tumors, performed Kaplan‐Meier survival analysis of lung adenocarcinoma (LUAD), explored the potential relationship between CDCA5 expression and clinicopathological characteristics, assessed the predictive capability of at different stages of clinicopathological characteristics, revealed the enriched functions and signaling pathways among LUAD paitents with high CDCA5 expression, and investigated the correlation between PD‐1, PD‐L1, and CDCA5 through bioinformatics analyses. Subsequently, we performed quantitative real‐time reverse transcription‐polymerase chain reaction (qRT‐PCR) and western blotting (WB) to demonstrate that CDCA5 mediates the p53‐p21 pathway and regulates the cell cycle.ResultCDCA5 is probably involved in the occurrence and development of NSCLC, and function as a reliable biomarker for predicting the survival outcomes of patients with early stage of patients with LUAD. Furthermore, CDCA5 may be a promising indicator of immunotherapy efficacy. In addition, silencing the expression of CDCA5 significantly increased the proportion of apoptotic NSCLC cells, and caused NSCLC cells to be arrested in the G1 phase.ConslusionIn conclusion, CDCA5 regulated the cell cycle of NSCLC cells by mediating the p53‐p21 signaling pathway, participating in the development and progression of NSCLC patients.

LncCDCA3L inhibits cell proliferation via a novel RNA structure-based crosstalk with CDCA3 in hepatocellular carcinoma.

The molecular mechanisms underlying hepatocellular carcinoma (HCC) remain poorly understood. In this study, we investigated cell division cycle-associated 3 (CDCA3) expression status and characterized a CDCA3-related long non-coding RNA (lncRNA) in HCC. RT-qPCR and western blot were used to determine CDCA3 expression level in HCC clinical specimens. 5' and 3'-RACE, RNAscope, RNA pull-down, CRISPR/Cas9-based RNA immunoprecipitation (CRIP) and site-directed mutation experiments were used to characterize lncCDCA3L and investigate its function target. Chi-square test and Kaplan-Meier analysis were used to assess lncCDCA3L clinical significance. The effects of lncCDCA3L on HCC development were assessed by overexpression in vitro and in vivo. In this study, we found CDCA3 was a potential oncogenic factor in HCC and characterized the lncCDCA3L, which could inhibit CDCA3. LncCDCA3L is significantly downregulated in HCC and its expression level is associated with tumour size and can act as an independent risk factor affecting postoperative survival time in HCC patients. Mechanistically, lncCDCA3L can repress CDCA3 protein level and inhibit hepatocarcinogenesis by directly binding to CDCA3 mRNA at 1423-1455 region via a novel manner based on a hairpin structure motif. Our study collectively unveiled the molecular mechanisms of how lncCDCA3L repressed the tumourigenic properties of HCC cells and exhibited a tumour suppressor character in HCC in a CDCA3-dependent manner. The findings here support lncCDCA3L can be used as a candidate prognostic biomarker for HCC patients.

CDCA8 Contributes to the Development and Progression of Thyroid Cancer through Regulating CDK1.

Background: This study aims to reveal regulatory role of cell division cycle associated 8 (CDCA8) in thyroid cancer progression and metastasis.Methods: A series of experiments in vivo and in vitro were performed to explore the function of CDCA8 in thyroid cancer.Results: Immunohistochemical analysis showed that CDCA8 expression levels were upregulated in thyroid cancer tissues compared with normal tissues, and were statistically correlated with tumor stage. Results of in vitro loss-of-function assay showed that downregulation of endogenous expression of CDCA8 could significantly inhibit cell proliferation, colony formation, cell migration, and promote apoptosis. Thyroid cancer cells lacking CDCA8 expression also had reduced tumorigenicity in vivo. Further, results of preliminary mechanistic exploration showed that CDK1 may be a potential downstream molecule of CDCA8 in regulating thyroid cancer progression. We subsequently confirmed that CDK1 itself exerted a significant regulatory function in thyroid cancer by loss- and gain-of-function experiments. Moreover, overexpression of CDK1 could weaken the tumor suppressive effect caused by CDCA8 knockdown.Conclusions: CDCA8 functions as an oncogene in thyroid cancer, and CDCA8 knockdown suppresses cancer development in vitro and in vivo. Additionally, CDK1 was further identified as a potential target of CDCA8 in thyroid cancer.

Suppression of CDCA3 inhibits prostate cancer progression via NF‑κB/cyclin D1 signaling inactivation and p21 accumulation.

Dysregulation of the cell cycle contributes to tumor progression. Cell division cycle-associated 3 (CDCA3) is a known trigger of mitotic entry and has been demonstrated to be constitutively upregulated in tumors. It is therefore associated with carcinogenic properties reported in various cancers. However, the role of CDCA3 in prostate cancer is unclear. In the present study, western blotting and analysis of gene expression profiling datasets determined that CDCA3 expression was upregulated in prostate cancer and was associated with a poor prognosis. CDCA3 knockdown in DU145 and PC-3 cells led to decreased cell proliferation and increased apoptosis, with increased protein expression levels of cleaved-caspase3. Further experiments demonstrated that downregulated CDCA3 expression levels induced G0/G1 phase arrest, which was attributed to increased p21 protein expression levels and decreased cyclin D1 expression levels via the regulation of NF-κB signaling proteins (NFκB-p105/p50, IKKα/β, and pho-NFκB-p65). In conclusion, these results indicated that CDCA3 may serve a crucial role in prostate cancer and consequently, CDCA3 knockdown may be used as a potential therapeutic target.

Prognostic value of CDCA3 in kidney renal papillary cell carcinoma

Kidney renal papillary cell carcinoma (KIRP) is a type of low-grade malignant renal cell carcinoma. Huge challenges remain in the treatment of KIRP. Cell division cycle associated 3 (CDCA3) participates in human physiological and pathological processes. However, its role in KIRP has not been established. Here, we evaluated the prognostic value of CDCA3 in KIRP using a comprehensive bioinformatics approach. Data for CDCA3 expression in KIRP were obtained from online database. Different expression genes between high and low CDCA3 expression groups were identified and evaluated by performing Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. A gene set enrichment analysis was performed to elucidate the function and pathway differences between the different. Differences in immune cell infiltration between low and high CDCA3 expression groups were analyzed by a single-sample GSEA method for immune cells. A protein-protein interaction network was generated and hub genes were identified. UALCAN was used to analyze associations between the mRNA expression levels of CDCA3 in KIRP tissues with clinicopathologic parameters. The diagnostic efficacy of CDCA3 for KIRP was analyzed by ROC analysis. Logistic regression was used to analyze relationships between the clinicopathological characteristics and CDCA3 expression. Our results indicated that high CDCA3 mRNA expression is significantly associated with some clinicopathologic parameters in KIRP patients High CDCA3 mRNA expression associated with a shorter overall survival, progression-free interval, and disease-special survival. Taken together, CDCA3 is a potential target for the development of anti-KIRP therapeutics and is an efficient prognostic marker.

Cell division cycle associated 8: A novel diagnostic and prognostic biomarker for hepatocellular carcinoma.

The cell division cycle associated 8 (CDCA8) is a crucial component of the chromosome passenger complex (CPC). It has been implicated in the regulation of cell dynamic localization during mitosis. However, its role in hepatocellular carcinoma (HCC) is not clearly known. In this study, data of 374 patients with HCC were retrieved from the Cancer Genome Atlas (TCGA) database. Pan analysis of Gene Expression Profiling Interactive Analysis (GEPIA) database was performed to profile the mRNA expression of CDCA8 in HCC. Then, the Kaplan‐Meier plotter database was analysed to determine the prognostic value of CDCA8 in HCC. In addition, samples of tumour and adjacent normal tissues were collected from 88 HCC patients to perform immunohistochemistry (IHC), reverse transcription‐quantitative polymerase chain reaction (qRT‐PCR) and Western blotting. The results obtained from bioinformatic analyses were validated through CCK‐8 assay, EdU assay, colony formation assay, cell cycle assays and Western blotting experiments. Analysis of the Kaplan‐Meier plotter database showed that high expression of CDCA8 may lead to poor overall survival (OS, p = 4.06e‐05) in patients with HCC. For the 88 patients with HCC, we found that stages and grades appeared to be strongly linked with CDCA8 expression. Furthermore, the high expression of CDCA8 was found to be correlated with poor OS (p = 0.0054) and progression‐free survival (PFS, p = 0.0009). In vitro experiments revealed that inhibition of CDCA8 slowed cell proliferation and blocked the cell cycle at the G0/G1 phase. In vivo experiments demonstrated that inhibition of CDCA8 inhibited tumour growth. Finally, blockade of CDCA8 reduced the expression levels of cyclin A2, cyclin D1, CDK4, CDK6, Ki67 and PCNA. And, there is an interaction between CDCA8 and E2F1. In conclusion, this research demonstrates that CDCA8 may serve as a biomarker for early diagnosis and prognosis prediction of HCC patients. In addition, CDCA8 could be an effective therapeutic target in HCC.

MiR-133a-3p inhibits the malignant progression of oesophageal cancer by targeting CDCA8.

The study aims to explore the interaction between miR-133a-3p and cell division cycle associated 8 (CDCA8) in oesophageal cancer (EC) and their effect on malignant behaviour of EC cells. Differential miRNAs and mRNAs were obtained from The Cancer Genome Atlas (TCGA) database. Quantitative real-time PCR (qRT-PCR) was used to detect the expression levels of miR-133a-3p and CDCA8 mRNA in EC cells. Western blot was used to detect the expression of CDCA8 protein. CCK-8, flow cytometry and Transwell assays were conducted to detect cell proliferation, cell cycle and apoptosis, as well as migration and invasion, respectively. The targeting relationship between miR-133a-3p and CDCA8 was verified by dual-luciferase reporter gene assay. In EC, miR-133a-3p expression was evidently low and CDCA8 expression was prominently high. MiR-133a-3p downregulated CDCA8 expression. A range of cell function experiments revealed that CDCA8 promoted the proliferation, migration and invasion of EC cells, reduced cell cycle arrest in G0/G1 phase and inhibited cell apoptosis, while miR-133a-3p could reverse the above effects by regulating CDCA8. MiR-133a-3p is a crucial tumour suppressor miRNA in EC, playing a tumour suppressor role by targeting CDCA8.

CDCA8 as an independent predictor for a poor prognosis in liver cancer

BackgroundHuman cell division cycle associated 8 (CDCA8) a key regulator of mitosis, has been described as a potential prognostic biomarker for a variety of cancers, such as breast, colon and lung cancers. We aimed to evaluate the potential role of CDCA8 expression in the prognosis of liver cancer by analysing data from The Cancer Genome Atlas (TCGA).MethodsThe Wilcoxon rank-sum test was used to compare the difference in CDCA8 expression between liver cancer tissues and matched normal tissues. Then, we applied logistic regression and the Wilcoxon rank-sum test to identify the association between CDCA8 expression and clinicopathologic characteristics. Cox regression and the Kaplan–Meier method were used to examine the clinicopathologic features correlated with overall survival (OS) in patients from the TCGA. Gene set enrichment analysis (GSEA) was performed to explore possible mechanisms of CDCA8 according to the TCGA dataset.ResultsCDCA8 expression was higher in liver cancer tissues than in matched normal tissues. Logistic regression and the Wilcoxon rank-sum test revealed that the increased level of CDCA8 expression in liver cancer tissues was notably related to T stage (OR = 1.64 for T1/2 vs. T3/4), clinical stage (OR = 1.66 for I/II vs. III/IV), histologic grade (OR = 6.71 for G1 vs. G4) and histological type (OR = 0.24 for cholangiocarcinoma [CHOL] vs. hepatocellular carcinoma [LIHC]) (all P-values < 0.05). Kaplan–Meier survival analysis indicated that high CDCA8 expression was related to a poor prognosis in liver cancer (P = 2.456 × 10−6). Univariate analysis showed that high CDCA8 expression was associated with poor OS in liver cancer patients, with a hazard ratio (HR) of 1.85 (95% confidence interval [CI]: 1.47–2.32; P = 1.16 × 10–7). Multivariate analysis showed that CDCA8 expression was independently correlated with OS (HR = 1.74; CI: 1.25–12.64; P = 1.27 × 10–5). GSEA revealed that the apoptosis, cell cycle, ErbB, MAPK, mTOR, Notch, p53 and TGF-β signaling pathways were differentially enriched in the CDCA8 high expression phenotype.ConclusionsHigh CDCA8 expression is a potential molecular predictor of a poor prognosis in liver cancer.