Cell Division Cycle Associated 5 Research Articles

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.

Cell division cycle associated 2 (CDCA2) upregulation promotes the progression of hepatocellular carcinoma in a p53-dependant manner.

BackgroundElevated expression and oncogenic functions of cell division cycle associated 2 (CDCA2), an important mitotic regulator, have been demonstrated in several cancer types, however their involvement in hepatocellular carcinoma (HCC) has not been elucidated, and the underlying molecular mechanism remains unclear. This study aims to determine the role of CDCA2 in HCC and the underlying molecular mechanism.MethodsThe expression of CDCA2 in HCC was studied in 40 pairs of frozen and 48 pairs of paraffin-embedded HCC samples and paracancerous normal samples by qRT-PCR and immunohistochemistry, respectively, and using The Cancer Genome Atlas (TCGA) datasets. The cellular function of CDCA2 was studied in vitro in the HepG2, Huh7 and SK-Hep1 HCC cell lines.ResultsWe found significantly upregulated CDCA2 expression in HCC, which was correlated with higher clinical stage, tumor grade and Glypican-3 (+). High CDCA2 expression was correlated with worse overall survival. CDCA2 promoted the proliferation of HCC cells by promoting G1/S transition through the upregulation and activation of CCND1/CDK4/6 and CCNE1/CDK2, enhanced the clonogenic ability, inhibited apoptosis in a p53/p21-dependent manner by inhibiting the p38 MAPK pathway and activating the JNK/c-Jun pathway, and promoted the migration of p53-mutant Huh7 cells by activating the epithelial-mesenchymal transition. Targeting CDCA2 reduced the chemoresistance of HCC cells to cisplatin. CDCA2 expression was also regulated by cyclophilin J.ConclusionsThis study revealed elevated expression of CDCA2 in HCC, possibly as a result of p53 dysregulation, which was associated with worse prognosis of patients. We confirmed the oncogenic role of CDCA2 in HCC in vitro and revealed some of the underlying molecular mechanisms. This study indicated the potential value of CDCA2 as a future target for the treatment of HCC.

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.

TPI1 activates the PI3K/AKT/mTOR signaling pathway to induce breast cancer progression by stabilizing CDCA5

BackgroundTriosephosphate isomerase 1 (TPI1), as a key glycolytic enzyme, is upregulated in multiple cancers. However, expression profile and regulatory mechanism of TPI1 in breast cancer (BRCA) remain mysterious.MethodsWestern blotting and immunohistochemistry (IHC) assays were used to investigate the expression of TPI1 in BRCA specimens and cell lines. TPI1 correlation with the clinicopathological characteristics and prognosis of 362 BRCA patients was analyzed using a tissue microarray. Overexpression and knockdown function experiments in cells and mice models were performed to elucidate the function and mechanisms of TPI1-induced BRCA progression. Related molecular mechanisms were clarified using co-IP, IF, mass spectrometric analysis, and ubiquitination assay.ResultsWe have found TPI1 is highly expressed in BRCA tissue and cell lines, acting as an independent indicator for prognosis in BRCA patients. TPI1 promotes BRCA cell glycolysis, proliferation and metastasis in vitro and in vivo. Mechanistically, TPI1 activates phosphoinositide 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway to regulate epithelial–mesenchymal transformation (EMT) and aerobic glycolysis, which is positively mediated by cell division cycle associated 5 (CDCA5). Moreover, TPI1 interacts with sequestosome-1 (SQSTM1)/P62, and P62 decreases the protein expression of TPI1 by promoting its ubiquitination in MDA-MB-231 cells.ConclusionsTPI1 promotes BRCA progression by stabilizing CDCA5, which then activates the PI3K/AKT/mTOR pathway. P62 promotes ubiquitin-dependent proteasome degradation of TPI1. Collectively, TPI1 promotes tumor development and progression, which may serve as a therapeutic target for BRCA.

Knockdown of CDCA5 suppresses malignant progression of breast cancer cells by regulating PDS5A.

Breast cancer is one of the most common malignant tumors in women. Cell division cycle-associated 5 (CDCA5) is closely associated with the behavior of various cancer types. The aim of the present study was to explore the effect of CDCA5 on breast cancer. Western blot analysis and reverse transcription-quantitative PCR were used to detect the expression level of CDCA5 in human normal mammary cells and human breast cancer cell lines. To determine its function in MDA-MB-231 cells, CDCA5 was silenced in MDA-MB-231 cells by transient short hairpin RNA transfection. Cell Counting Kit-8 and clonogenicity assays were used to evaluate cell proliferation. Wound healing and Transwell assays were used to detect cell invasion and migration. Western blot analysis was used to detect the protein expressions of Ki67 and PCNA associated with proliferation, MMP2 and MMP9 associated with migration. CDCA5 was found to be markedly increased in breast cancer cell lines. CDCA5 knockdown was able to suppress cell proliferation, invasion and migration. CDCA5 inhibition downregulated PDS5 cohesin-associated factor A (PDS5A) expression in breast cancer cells. PDS5A overexpression was found to reverse the effect of CDCA5 inhibition on breast cancer cell proliferation and migration. CDCA5 knockdown was shown to suppress the malignant progression of breast cancer cells by regulating PDS5A. The present findings may provide new potential targets for breast cancer therapy.

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.

Methylation-dependent and -independent roles of EZH2 synergize in CDCA8 activation in prostate cancer.

Cell division cycle-associated 8 (CDCA8) is a component of chromosomal passenger complex (CPC) that participates in mitotic regulation. Although cancer-related CDCA8 hyperactivation has been widely observed, its molecular mechanism remains elusive. Here, we report that CDCA8 overexpression maintains tumorigenicity and is associated with poor clinical outcome in patients with prostate cancer (PCa). Notably, enhancer of zeste homolog 2 (EZH2) is identified to be responsible for CDCA8 activation in PCa. Genome-wide assays revealed that EZH2-induced H3K27 trimethylation represses let-7b expression and thus protects the let-7b-targeting CDCA8 transcripts. More importantly, EZH2 facilitates the self-activation of E2F1 by recruiting E2F1 to its own promoter region in a methylation-independent manner. The high level of E2F1 further promotes transcription of CDCA8 along with the other CPC subunits. Taken together, our study suggests that EZH2-mediated cell cycle regulation in PCa relies on both its methyltransferase and non-methyltransferase activities.

Silencing CDCA8 inhibits the proliferation and invasion of gastric cancer cells and induces apoptosis by blocking the Akt pathway

&#x0D; &#x0D; &#x0D; &#x0D; Purpose: To investigate the effect of cell division cycle associated 8 (CDCA8) on malignant progression of gastric cancer (GC) cells.&#x0D; Methods: Short hairpin RNAs (shRNA) were transfected into two gastric cell lines to knock down expression of CDCA8. Transfection efficiency was analyzed using quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Then, Cell Counting Kit 8 and colony formation and Transwell assays were utilized to explore the effect of CDCA8 knockdown on the proliferation, invasion, and migration of GC cells. Flow cytometry was conducted to analyze the effect of CDCA8 knockdown on cell cycle progression and apoptosis. The relationship between CDCA8, epithelial-mesenchymal transition (EMT), and Akt pathway activity was determined by western blot analysis.&#x0D; Results: Proliferation, invasion, and migration of GC cells were significantly inhibited by CDCA8 knockdown. Knockdown of CDCA8 induced cell cycle arrest in G1 phase and apoptosis, and inhibited EMT and Akt pathway activity.&#x0D; Conclusion: Knockdown of CDCA8 inhibits GC growth and metastasis in vitro by reducing Akt pathway activity. Thus, this molecule presents a potential strategy for the management of GC.&#x0D; &#x0D; &#x0D; &#x0D;

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.

Identification of CDCA2 as a Diagnostic and Prognostic Marker for Hepatocellular Carcinoma.

ObjectiveHepatocellular carcinoma (HCC) is one of the most common and malignant tumors with an insidious onset, difficult early diagnosis, and limited therapy options, resulting in a poor prognosis. Cell division cycle associated 2 (CDCA2), also known as Repo-Man, plays an important role in regulating mitosis and DNA repair, but the involvement of CDCA2 in HCC remains unclear.MethodsThe differentially expressed genes that were significantly upregulated in multiple RNA sequencing datasets of HCC were screened. Receiver operating characteristic (ROC) curve analysis was performed to identify diagnostic markers for HCC. Least absolute shrinkage and selection operator Cox regression analysis was performed to screen the prognosis-related genes. The screening and analyses identified CDCA2 as the target gene in this study. The expression of CDCA2 was analyzed in public databases and clinical specimens, and CDCA2 involvement in HCC was explored by both bioinformatic analysis and in vitro experiments.ResultsThe level of CDCA2 was enhanced in HCC compared with healthy livers. Overexpression of CDCA2 positively correlated with the pathological grade and TNM stage of the diseases. Furthermore, CDCA2 was found to be an independent prognostic predictor. An excellent prognostic model of HCC was successfully constructed with CDCA2 in combination with TNM stage. Bioinformatic analysis revealed that CDCA2 was closely associated with the cell cycle, apoptosis, and p53 signaling pathway. Silencing CDCA2 in Huh7 cells resulted in significant upregulation of p53 and the downstream PUMA and NOXA and a subsequently increased apoptosis. Inhibition of p53 signaling and apoptosis was found after overexpression of CDCA2 in L02 cells. Strikingly, the proliferation of cells was not affected by CDCA2.ConclusionsCDCA2 was a novel diagnostic marker for HCC, and overexpression of this gene reflected poor pathological grade, stage, and clinical prognosis. CDCA2 promoted the pathogenesis of HCC by suppressing the p53-PUMA/NOXA signaling and the subsequent apoptosis.

SPOP promotes CDCA5 degradation to regulate prostate cancer progression via the AKT pathway.

The E3 ubiquitin ligase adaptor Speckle-type POZ protein (SPOP) plays an important tumour suppressor role in prostate cancers (PCa), with mutation rate up to 15%. However, how SPOP mutations regulate prostate tumorigenesis remains elusive. Here, we report the identification of cell division cycle associated 5 (CDCA5) as a SPOP substrate. We found that SPOP interacts with CDCA5 and promotes its polyubiquitin degradation in a degron-dependent manner. This effect was greatly impaired by introducing PCa associated SPOP mutations. Importantly, we found that CDCA5 was essential for PCa cells to survive and proliferate. CDCA5 depletion in PCa cells led to cessation of proliferation, G2M arrest, severe sister chromatid aggregation disturbance, and apoptosis. we also found that CDCA5 knockdown decreased the protein expression of p-GSK3β, increased the activity of caspase-3, caspase-9, and the Bax/Bcl-2 ratio. Besides, we confirmed that CDCA5 interrupted cancer cell behavior via the AKT pathway. In contrast, silencing SPOP or overexpressing CDCA5 increased cell proliferation. Consistently, depleting SPOP along with CDCA5, or overexpressing CDCA5 along with SPOP also caused the growth of cells repressed. Consistent with the functional role of CDCA5, the mRNA and protein levels of CDCA5 were significantly increased in PCa, compared to normal tissues, and its high expression was associated with more severe lymph node metastasis, higher Gleason score, and poorer prognosis. Together, our data showed that SPOP plays a crucial role in inhibiting tumorigenesis and partly achieved this by promoting the degradation of oncoprotein CDCA5.

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.

CDCA2 promotes tumorigenesis and induces radioresistance in oesophageal squamous cell carcinoma cells.

Cell division cycle-associated 2 (CDCA2) overexpression has been demonstrated to serve a significant role in tumorigenesis in certain types of cancer. Nevertheless, its role in tumour proliferation and radioresistance in oesophageal squamous cell carcinoma (ESCC) remains to be elucidated. Thus, the present study aimed to elucidate these roles. Data were downloaded from The Cancer Genome Atlas (TCGA) to compare the gene expression profiles. The expression of CDCA2 was higher in ESCC tissues compared with normal tissues. Gene set enrichment analysis was performed based on the ESCC cohorts in TCGA database. This demonstrated that higher expression of CDCA2 was significantly associated with the expression of related components of the cell cycle phase transition and G2/M phase transition pathways. Collectively, the results revealed that CDCA2 could serve as an underlying target to regulate tumour growth and radioresistance among patients with ESCC.

LINC01515 promotes nasopharyngeal carcinoma progression by serving as a sponge for miR-325 to up-regulate CDCA5.

Long non-coding RNAs (LncRNAs) have gained widespread interest and attention as vital regulators in cancer occurrence and development. Nonetheless, the functions and mechanisms of lncRNAs involved in nasopharyngeal carcinoma (NPC) are largely unknown. By analysing the data from GSE61218, we identified a novel lncRNA LINC01515 which is altered in NPC. A series of experiments were performed to examine the exact roles of LINC01515 as well as the molecular mechanisms by which LINC01515 acted in NPC. LINC01515 expression was increased in NPC and that high LINC01515 expression was associated with a worse prognosis. Functionally, depletion of LINC01515 resulted in an inhibition of cell proliferation, migration and invasion, while apoptosis was promoted. Mechanistically, LINC01515 facilitated cell division cycle associated 5 (CDCA5) expression via serving as a sponge for miR-325. And more notably, miR-325 suppressed NPC progression in vitro by targeting CDCA5. Furthermore, the anti-tumor property induced by LINC01515 knockdown was partially reversed due to the overexpression of CDCA5. Taken together, LINC01515 exerted the carcinogenic effect in NPC through regulating miR-325/CDCA5 pathway. Our findings shed light on the possibility of exploiting LINC01515 as a prognostic biomarker or therapeutic target in NPC.