Cyclin B2 impairs the p53 signaling in nasopharyngeal carcinoma.

BACKGROUND: Cyclin B2 (CCNB2), a member of the cyclin family, is an oncogene in multiple cancers, including nasopharyngeal carcinoma (NPC). However, the epigenetics mechanism for CCNB2 overexpression in NPC remains unclear. This study dissects the regulatory role of CCNB2 in NPC and the molecular mechanism. METHODS: Differentially methylated genes (DMG) and differentially expressed genes (DEG) were screened out in GSE52068 and GSE13597 databases, respectively, and candidate targets were identified by the Venn diagram. GO annotation and pathway enrichment analyses were performed on selected DMG and DEG, and a PPI network was constructed to pinpoint hub genes. PCR and qMSP were conducted to detect the expression and methylation of CCNB2 in cells. The siRNA targeting CCNB2 was transfected into NPC cells, and the migration, proliferation, cell cycle, epithelial-mesenchymal transition (EMT), tumorigenesis, and metastasis were examined. The upstream factor responsible for CCNB2 overexpression in NPC was explored. The p53 activity in NPC cells was assessed using western blot analysis. RESULTS: CCNB2 showed hypomethylation and overexpression in NPC. CCNB2 silencing inhibited cell migration, proliferation, cell cycle entry, and EMT. JMJD6 was overexpressed in NPC and upregulated CCNB2 through demethylation. JMJD6 reversed the effects of CCNB2 downregulation, resulting in elevated cellular activity in vitro and tumorigenic and metastatic activities in vivo. CCNB2 blocked the p53 pathway, while the p53 pathway inhibitor reversed the effect of CCNB2 silencing to increase the activity of NPC cells. CONCLUSIONS: JMJD6 enhanced CCNB2 transcription by demethylating CCNB2, thereby repressing the p53 pathway and promoting NPC progression.

Extracellular vesicle-derived CircWhsc1 promotes cardiomyocyte proliferation and heart repair by activating TRIM59/STAT3/Cyclin B2 pathway.

INTRODUCTION: Extracellular vesicles (EVs)-mediated cell-to-cell communication is crucial for hypoxia-induced cell proliferation and tissue repair, but its function in endogenous cardiac regeneration is still unknown. OBJECTIVES: Herein, we aimed to determine whether hypoxia-inducible circWhsc1 in endothelial EVs promoted cardiomyocyte (CM) proliferation and cardiac regeneration. METHODS: RNA-sequence data was used to identify EV circRNAs that were involved into endogenous cardiac regeneration. Quantitative polymerase chain reactions were conducted to determine circRNA expression in tissue, cells and EVs. Gain- and loss-of-function assays were performed to explore the function of EV-derived circWhsc1 during cardiac regeneration. Western blotting and RNA pulldown assays were used to investigate its underlying mechanism. RESULTS: We found that circWhsc1 was enriched in neonatal mouse hearts, particularly in cardiac ECs, and was further upregulated both in ECs and EC-derived EVs under hypoxic conditions. When cocultured with hypoxia-preconditioned neonatal ECs or their secreted EVs, both neonatal and adult CMs exhibited an increased proliferation rate and G2/M ratio, which could be attenuated by knockdown of circWhsc1 in ECs. In vivo, EC-restricted overexpression of circWhsc1 and EV-mediated delivery of circWhsc1 induced CM proliferation, alleviated cardiac fibrosis and restored cardiac function following myocardial infarction in adult mice. Mechanistic studies revealed that EV-derived circWhsc1 activated TRIM59 by enhancing its phosphorylation, thereby reinforcing the binding of TRIM59 to STAT3, phosphorylating STAT3 and inducing CM proliferation. CONCLUSION: The current study demonstrated that hypoxia-inducible circWhsc1 in EC-derived EVs induces CM proliferation and heart regeneration. EC-CM communication mediated by EV-derived circWhsc1 might represent a prospective therapeutic target for inducing cardiac repair post-myocardial infarction.

CCNB1 and CCNB2 involvement in the pathogenesis of psoriasis: a bioinformatics study.

OBJECTIVE: The cell cycle-related proteins cyclin B1 (CCNB1) and cyclin B2 (CCNB2) are potentially involved in the underlying mechanisms of psoriasis. The present study aimed to explore this possibility using bioinformatics approaches. METHODS: CCNB1 and CCNB2 protein levels were evaluated in 14 psoriasis patients and five healthy controls by enzyme-linked immunosorbent assays, and their mRNA levels were evaluated using data from four publicly available datasets (GSE53552, GSE41664, GSE14905, and GSE13355). Comparison of high- and low-expressing groups were performed to reveal CCNB1- and CCNB2-related differentially expressed genes, which were then assessed based on gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. Correlation analyses between CCNB1 and CCNB2 levels and immune infiltration, as well as typical targets of psoriasis, were also performed. RESULTS: Overall, 12 CCNB1 and CCNB2 common immune-related targets potentially involved in psoriasis were identified. These could regulate the cell cycle of through multiple pathways. In addition, CCNB1 and CCNB2 were found to potentially support the release of key molecular targets of psoriasis through the regulation of mast cell activation and macrophage polarization. CONCLUSIONS: These findings suggest that CCNB1 and CCNB2 may represent valuable molecular biomarkers of psoriasis, contributing to its onset and progression.

Hsa_circ_0000285 knockdown inhibits the progression of hepatocellular carcinoma by sponging miR-582-3p to regulate CCNB2 expression.

AIM: Hsa_circ_0000285, a novel circular RNA, has been proven to extensively take part in the pathogenesis of numerous tumors. In hepatocellular carcinoma (HCC), very little is known about hsa_circ_0000285 until now. Hence, this research aims to determine hsa_circ_0000285's functional role and underlying mechanisms in HCC. METHODS: The expressions of miR-582-3p, hsa_circ_000028, and cyclin B2 (CCNB2) among the HCC cells and tumor samples were determined by performing western blotting and qRT-PCR analyses. The impacts of hsa_circ_000028 on the proliferative and migratory abilities of HCC cells were examined through the execution of CCK-8 and wound-healing assays. Meanwhile, the expressions of the proteins Bcl-2 and Bax were detected via western blotting. Tumor xenograft models were established to examine how hsa_circ_000028 functions during the mediation of HCC tumor growth in vivo. RNA immunoprecipitation and luciferase reporter experiments were performed for the validation of the interactions of miR-582-3p, hsa_circ_000028, and CCNB2 with each other. RESULTS: Elevated hsa_circ_0000285 and CCNB2 expressions, and a decreased miR-582-3p expression were observed among the HCC cell lines and tumors. Hsa_circ_0000285 bound to miR-582-3p competitively to improve CCNB2 levels. Silencing of hsa_circ_0000285 promoted apoptosis and repressed proliferation and migration among HCC cells. Moreover, silencing hsa_circ_0000285 also impeded the growth of HCC tumors in vivo. Inhibiting hsa_circ_0000285 or CCNB2 reversed the miR-582-3p-knockdown-mediated promotion of malignant HCC cell phenotypes. CONCLUSION: Our study has demonstrated that hsa_circ_0000285 fosters the development of malignant HCC cells phenotypes through the modulation of the miR-582-3p/CCNB2 axis. Thus, these results suggest that hsa_circ_0000285 is a prospective target for HCC treatment.

Mad2 promotes Cyclin B2 recruitment to the kinetochore for guiding accurate mitotic checkpoint.

Accurate mitotic progression relies on the dynamic phosphorylation of multiple substrates by key mitotic kinases. Cyclin-dependent kinase 1 is a master kinase that coordinates mitotic progression and requires its regulatory subunit Cyclin B to ensure full kinase activity and substrate specificity. The function of Cyclin B2, which is a closely related family member of Cyclin B1, remains largely elusive. Here, we show that Mad2 promotes the kinetochore localization of Cyclin B2 and that their interaction at the kinetochores guides accurate chromosome segregation. Our biochemical analyses have characterized the Mad2-Cyclin B2 interaction and delineated a novel Mad2-interacting motif (MIM) on Cyclin B2. The functional importance of the Cyclin B2-Mad2 interaction was demonstrated by real-time imaging in which MIM-deficient mutant Cyclin B2 failed to rescue the chromosomal segregation defects. Taken together, we have delineated a previously undefined function of Cyclin B2 at the kinetochore and have established, in human cells, a mechanism of action by which Mad2 contributes to the spindle checkpoint.

Cyclin B2 overexpression promotes tumour growth by regulating jagged 1 in hepatocellular carcinoma.

BACKGROUND: Our previous study showed that Cyclin B2 (CCNB2) is closely related to the occurrence and progression of hepatocellular carcinoma (HCC). AIM OF THE STUDY: This study aimed to clarify the effect of CCNB2 gene silencing on tumorigenesis in nude mice and to detect the potential mechanism. METHODS: The effect of CCNB2 on HCC was tested in vivo. The downstream target genes of CCNB2 were predicted by proteomics and confirmed by western blot assay. The regulatory functions of CCNB2 in the proliferation and migration of HCC cells were determined through functional recovery experiments. The expression of the downstream target genes of CCNB2 was detected by immunohistochemistry. RESULTS: Knockdown of CCNB2 decreased tumour formation rate and tumour volume and weight and inhibited tumour proliferation. A total of 130 differentially expressed proteins were detected by proteomics, and Jagged 1 (JAG1) was predicted as the potential downstream target of CCNB2. Western blot assay revealed that CCNB2 and JAG1 expression was significantly correlated in HCC cells. The results of functional recovery experiments suggested that CCNB2 knockdown weakened the proliferation and migration ability of HCC cells, while JAG1 overexpression restored this ability of HCC cells that was weakened by CCNB2 knockdown. Immunohistochemistry showed that JAG1 expression was higher in HCC tissues than in paracancerous tissues and was related to tumour size and number and tumour thrombus formation. CONCLUSIONS: The proliferation of HCC cells in vivo was inhibited by CCNB2 knockdown. CCNB2 may accelerate the proliferation and metastasis of HCC cells by increasing JAG1 expression.

Protective role of m6A binding protein YTHDC2 on CCNB2 in manganese-induced spermatogenesis dysfunction.

Human infertility has become the third largest serious disease in the world, seriously affecting the quality of human fertility. Studies have shown that manganese (Mn) can accumulate in the testis through the blood-testicular barrier and damage the male reproductive system. However, the mechanism has not been explored clearly. Recent studies have reported that YTH domain-containing 2 (YTHDC2) can regulate reproductive function. However, none has explored the role of YTHDC2 in Mn-induced reproductive toxicity. The present study investigated whether YTHDC2/CyclinB2 (CCNB2) pathway participates in Mn-induced reproductive toxicity using Kunming mice, spermatogonia, and the seminal plasma of male workers. The mice were received intraperitoneal (i.p.) injections of 0, 12.5, 25, and 50 mg/kg MnCl2 once daily for 2 weeks. The cells were treated with 0, 100, 200 and 400 µM MnCl2 for 24 h. Here, we found that occupational Mn exposure significantly increased Mn levels in the seminal plasma of male workers, while decreased sperm density, semen quality, and the levels of YTHDC2, CCNB1, and CCNB2. We found that Mn can inhibit the YTHDC2/CCNB2 signaling pathway and block the G2/M phase of the cell cycle. Moreover, the morphology of cells and the histomorphology of mice testis were injured. Notably, over-expression (OE) of YTHDC2 increased CCNB2 levels, reduced cell cycle arrest, and improved reproductive toxicity after Mn exposure. These findings suggest that the YTHDC2/CCNB2 signaling pathway participates in Mn-induced reproductive toxicity, and OE of YTHDC2 can mitigate the toxicity of Mn.

Cyclin-dependent kinase 1 as a potential target for lycorine against hepatocellular carcinoma.

The pathological changes and possible underlying molecular mechanisms of hepatocellular carcinoma (HCC) are currently unclear. Effective treatment of this pathological state remains a challenge. The purpose of this study is to obtain some key genes with diagnostic and prognostic meaning and to identify potential therapeutic agents for HCC treatment. Here, CDK1, CCNB1 and CCNB2 were found to be highly expressed in HCC patients and accompanied by poor prognosis, and knockdown of them by siRNA drastically induced autophagy and senescence in hepatoma cells. Simultaneously, the anti-HCC effect of lycorine was comparable to that of interfering with these three genes, and lycorine significantly promoted the decrease both in protein and mRNA expression of CDK1. Molecular validation mechanistically demonstrated that lycorine might attenuate the degradation rate of CDK1 via interaction with it, which had been confirmed by cellular thermal shift assay and drug affinity responsive targets stability assay. Taken together, these findings suggested that CDK1, CCNB1 and CCNB2 could be regarded as potential diagnostic and prognostic biomarkers for HCC, and CDK1 might serve as a promising therapeutic target for lycorine against HCC.

CCNB2/SASP/Cathepsin B & PGE2 Axis Induce Cell Senescence Mediated Malignant Transformation.

Glioma is the most frequent and aggressive adult brain tumor with maximum mortality. However, the gene alteration and mechanism underlying malignant transformation of glioma remain largely unknown. We aimed to find key factors regulating tumor progression and malignant transformation of glioma. Here we compared the gene expression profiles of 693 glioma patients by HGG vs. LGG model, and identified a key factor CCNB2 for malignant transformation in glioma. CCNB2 induced a senescence-associated secretory phenotype (SASP) of glioma cells, and the malignant progression, such as invasion and excessive proliferation was mediated by secreting SASP cytokines, Cathepsin B and PGE2. These findings demonstrated a previously undiscovered link between senescence, CCNB2/SASP/Cathepsin B & PGE2 axis and malignant transformation in glioma. This might provide novel insights on developing new therapeutic regimens for abrogating aggressiveness of glioma.

Cyclin B2 (CCNB2) Stimulates the Proliferation of Triple-Negative Breast Cancer (TNBC) Cells In Vitro and In Vivo.

Triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer. Currently, targeting therapy makes great advances for the treatment of TNBC, whereas more effective therapeutic targets are urgently needed. Cyclin B2 (CCNB2), which belongs to B-type cyclins, is known as a cell cycle regulator. CCNB2 is synthesized at G1 phase in cancer cells and downregulated at anaphase. The defects of CCNB2 led to the abnormal cell cycle and tumorigenesis. Though there are wide effects of CCNB2 on multiple types of tumors, the potential role of CCNB2 in TNBC progression is still unclear. Herein, we found that CCNB2 was highly expressed in human TNBC tissues and correlated with the prognosis and clinical pathological features including tumor size (p = 0.022∗) and pTNM stage (p = 0.021∗) of patients with TNBC. CCNB2 could promote the proliferation of TNBC cells in vitro and in mice. Our findings therefore confirmed the involvement of CCNB2 in TNBC progression and provided the evidence that CCNB2 could serve as a promising molecular target of TNBC.

Two cyclin Bs are differentially modulated by glucose and sucrose during maize germination.

Cell proliferation during seed germination is determinant for an appropriate seedling establishment. The present work aimed to evaluate the participation of two maize B-type Cyclins during germination and under the stimulus of two simple sugars: sucrose and glucose. We found out that the corresponding genes, ZmCycB1;2 and ZmCycB2;1, increased their expression at 24 h of germination, but only ZmCycB1;2 responded negatively to sugar type at the highest sugar concentration tested (120 mM). Also, CycB1;2 showed differential protein levels along germination in response to sugar, or its absence. Both CycBs interacted with CDKA;1 and CDKB1;1 by pull down assays. By an immunoprecipitation approach, it was found that each CycB associated with two CDKB isoforms (34 and 36 kDa). A higher proportion of CycB1;2-CDKB-36kDa was coincident to an increased kinase activity in the presence of sugar and particularly in glucose treatment at 36 h of imbibition. CycB1;2-CDKB activity increased in parallel to germination advance and this was dependent on sugar: glucose > sucrose > No sugar treatment. At RAM, CycB1;2 was more abundant in nuclei on Glucose at late germination; DNA-CycB1;2 colocalization was parallel to CycB1;2 inside the nucleus. Overall, results point out CycB1;2 as a player on promoting proliferation during germination by binding a specific CDKB isoform partner and changing its cellular localization to nuclei, co-localizing with DNA, being glucose a triggering signal.

CCNB2, TOP2A, and ASPM Reflect the Prognosis of Hepatocellular Carcinoma, as Determined by Weighted Gene Coexpression Network Analysis.

BACKGROUND: Hepatocellular carcinoma (HCC) is characterized by increased mortality and poor prognosis. We aimed to identify potential prognostic markers by weighted gene coexpression network analysis (WGCNA), to assist clinical outcome prediction and improve treatment decisions for HCC patients. METHODS: Prognosis-related gene modules were first established by WGCNA. Venn diagrams obtained intersection genes of module genes and differentially expressed genes. The Kaplan-Meier overall survival curves and disease-free survival curves of intersection genes were further analyzed on the Gene Expression Profiling Interactive Analysis website. Chi-square tests were performed to explore the associations between prognostic gene expressions and clinicopathological features. RESULTS: CCNB2, TOP2A, and ASPM were identified as both prognosis-related genes and differentially expressed genes. TOP2A (HR: 1.7, P = 0.003) and ASPM (HR: 1.8, P < 0.001) exhibited a significant difference between the high- and low-expression groups in the overall survival analysis, while CCNB2 (HR: 1.4, P = 0.052) was not statistically significant. CCNB2 (HR: 1.5, P = 0.006), TOP2A (HR: 1.7, P < 0.001), and ASPM (HR: 1.6, P = 0.003) were all statistically significant in the disease-free survival analysis. All three genes were significantly associated with race and fetoprotein values (P < 0.05). CCNB2 expression was associated with tumor stage (P = 0.01), and ASPM expression was associated with new tumor events (P = 0.03). CONCLUSION: Overexpression of CCNB2, TOP2A, and ASPM are associated with poor prognosis, and these genes could serve as potential prognostic markers and therapeutic targets for HCC.

CCNB2 and AURKA overexpression may cause atypical mitosis in Japanese cortisol-producing adrenocortical carcinoma with TP53 somatic variant.

BACKGROUND: Many genomic analyses of cortisol-producing adrenocortical carcinoma (ACC) have been reported, but very few have come from East Asia. The first objective of this study is to verify the genetic difference with the previous reports by analyzing targeted deep sequencing of 7 Japanese ACC cases using next-generation sequencing (NGS). The second objective is to compare the somatic variant findings identified by NGS analysis with clinical and pathological findings, aiming to acquire new knowledge about the factors that contribute to the poor prognosis of ACC and to find new targets for the treatment of ACC. METHOD: DNA was extracted from ACC tissue of seven patients and two reference blood samples. Targeted deep sequencing was performed using the MiSeq system for 12 genes, and the obtained results were analyzed using MuTect2. The hypothesis was obtained by integrating the somatic variant findings with clinical and pathological data, and it was further verified using The Cancer Genome Atlas (TCGA) dataset for ACC. RESULTS: Six possible pathogenic and one uncertain significance somatic variants including a novel PRKAR1A (NM_002734.4):c.545C>A (p.T182K) variant were found in five of seven cases. By integrating these data with pathological findings, we hypothesized that cases with TP53 variants were more likely to show atypical mitotic figures. Using TCGA dataset, we found that atypical mitotic figures were associated with TP53 somatic variant, and mRNA expression of CCNB2 and AURKA was significantly high in TP53 mutated cases and atypical mitotic figure cases. CONCLUSION: We believe this is the first report that discusses the relationship between atypical mitotic figures and TP53 somatic variant in ACC. We presumed that overexpression of CCNB2 and AURKA mRNA may cause atypical mitosis in TP53 somatic mutated cases. Because AURKA is highly expressed in atypical mitotic cases, it may be an appropriate indicator for AURKA inhibitors.

MicroRNA-582-3p negatively regulates cell proliferation and cell cycle progression in acute myeloid leukemia by targeting cyclin B2.

BACKGROUND: MicroRNAs (miRNAs) function as post-transcriptional gene expression regulators. Some miRNAs, including the recently discovered miR-582-3p, have been implicated in leukemogenesis. This study aimed to reveal the biological function of miR-582-3p in acute myeloid leukemia (AML), which is one of the most frequently diagnosed hematological malignancies. METHODS: The expression of miR-582-3p was determined using quantitative real-time PCR in blood samples from leukemia patients and in cell lines. Cell proliferation and cell cycle distribution were analyzed using the CCK-8, colony formation and flow cytometry assays. The target gene of miR-582-3p was verified using a dual-luciferase reporter assay. The G2/M phase arrest-related molecule contents were measured using western blotting analysis. RESULTS: We found miR-582-3p was significantly downregulated in the blood samples from leukemia patients and in the cell lines. MiR-582-3p overexpression significantly impaired cell proliferation and induced G2/M cell cycle arrest in THP-1 cells. Furthermore, cyclin B2 (CCNB2) was confirmed as a target gene of miR-582-3p and found to be negatively regulated by miR-582-3p overexpression. More importantly, CCNB2 knockdown showed suppressive effects on cell proliferation and cell cycle progression similar to those caused by miR-582-3p overexpression. The inhibitory effects of miR-582-3p overexpression on cell proliferation and cell cycle progression were abrogated by CCNB2 transfection. CONCLUSION: These findings indicate new functions and mechanisms for miR-582-3p in AML development. Further study could clarify if miR-582-3p and CCNB2 are potential therapeutic targets for the treatment of AML.

The cyclin B2/CDK1 complex inhibits separase activity in mouse oocyte meiosis I.

Chromosome segregation is driven by separase, activity of which is inhibited by binding to securin and cyclin B1/CDK1. In meiosis, premature separase activity will induce aneuploidy or abolish chromosome segregation owing to the untimely destruction of cohesin. Recently, we have proved that cyclin B2 can compensate for cyclin B1 in CDK1 activation for the oocyte meiosis G2/M transition. In the present study, we identify an interaction between cyclin B2/CDK1 and separase in mouse oocytes. We find that cyclin B2 degradation is required for separase activation during the metaphase I-anaphase I transition because the presence of stable cyclin B2 leads to failure of homologous chromosome separation and to metaphase I arrest, especially in the simultaneous absence of securin and cyclin B1. Moreover, non-phosphorylatable separase rescues the separation of homologous chromosomes in stable cyclin B2-arrested cyclin B1-null oocytes. Our results indicate that cyclin B2/CDK1 is also responsible for separase inhibition via inhibitory phosphorylation to regulate chromosome separation in oocyte meiosis, which may not occur in other cell types.

Cycling through mammalian meiosis: B-type cyclins in oocytes.

B-type cyclins in association with Cdk1 mediate key steps of mitosis and meiosis, by phosphorylating a plethora of substrates. Progression through the meiotic cell cycle requires the execution of two cell divisions named meiosis I and II without intervening S-phase, to obtain haploid gametes. These two divisions are highly asymmetric in the large oocyte. Chromosome segregation in meiosis I and sister chromatid segregation in meiosis II requires the sharp, switch-like inactivation of Cdk1 activity, which is brought about by degradation of B-type cyclins and counteracting phosphatases. Importantly and contrary to mitosis, inactivation of Cdk1 must not allow S-phase to take place at exit from meiosis I. Here, we describe recent studies on the regulation of translation and degradation of B-type cyclins in mouse oocytes, and how far their roles are redundant or specific, with a special focus on the recently discovered oocyte-specific role of cyclin B3.

Cyclin B2 Overexpression in Human Hepatocellular Carcinoma is Associated with Poor Prognosis.

BACKGROUND AND AIMS: Cyclin B2 (CCNB2) has been reported to be highly expressed in a few malignancies. However, the biological function of CCNB2 in hepatocellular carcinoma (HCC) is largely unknown. We aimed to investigate the effect of CCNB2 in HCC. METHODS: The expression of CCNB2 in HCC and normal liver tissues and connection of its expression with prognosis and clinical parameters were studied. The effect of knocking down CCNB2 on cell proliferation, migration, cell cycle distribution, and apoptosis were estimated in BEL-7404 cells. RESULTS: Compared to normal liver tissues, the level of CCNB2 was higher in HCC tissues from the Gene Expression Profiling Interactive Analysis (GEPIA). The 5 year overall survival and disease-free survival of HCC patients with high CCNB2 levels were shorter than that of those with low CCNB2 levels. Immunohistochemistry analysis also discovered the expression differences of CCNB2 in HCC and normal liver tissues and showed that CCNB2 expression was significantly associated with tumor number, tumor size, tumor thrombus, and alanine aminotransferase level. CCNB2 expression was higher in HCC cell lines (BEL-7404, Hep3B, BEL-7402, and SMMC-7721) than that in the normal hepatic cell line (HL-7702). Knockdown of CCNB2 inhibited cell proliferation and migration, promoted cell apoptosis, and caused S phase arrest in BEL-7404 cells. Finally, CCNB2 was associated with Polo Like Kinase 1 (PLK1) in the GEPIA database and BEL-7404 cells. CONCLUSIONS: CCNB2 may serve as a prognostic factor and participated in the development and progression and promote cell proliferation and migration through CCNB2/PLK1 pathway in HCC.

Cyclin B2 is required for progression through meiosis in mouse oocytes.

Cyclins associate with cyclin-dependent serine/threonine kinase 1 (CDK1) to generate the M phase-promoting factor (MPF) activity essential for progression through mitosis and meiosis. Although cyclin B1 (CCNB1) is required for embryo development, previous studies concluded that CCNB2 is dispensable for cell cycle progression. Given previous findings of high Ccnb2 mRNA translation rates in prophase-arrested oocytes, we re-evaluated the role of this cyclin during meiosis. Ccnb2-/- oocytes underwent delayed germinal vesicle breakdown and showed defects during the metaphase-to-anaphase transition. This defective maturation was associated with compromised Ccnb1 and Moloney sarcoma oncogene (Mos) mRNA translation, delayed spindle assembly and increased errors in chromosome segregation. Given these defects, a significant percentage of oocytes failed to complete meiosis I because the spindle assembly checkpoint remained active and anaphase-promoting complex/cyclosome function was inhibited. In vivo, CCNB2 depletion caused ovulation of immature oocytes, premature ovarian failure, and compromised female fecundity. These findings demonstrate that CCNB2 is required to assemble sufficient pre-MPF for timely meiosis re-entry and progression. Although endogenous cyclins cannot compensate, overexpression of CCNB1/2 rescues the meiotic phenotypes, indicating similar molecular properties but divergent modes of regulation of these cyclins.

Bioinformatics analysis of the prognostic value of CCT6A and associated signalling pathways in breast cancer.

Breast cancer (BC) is the most frequently diagnosed type of cancer and the leading cause of cancer­associated mortality among women worldwide. However, the molecular basis for the pathogenesis of BC requires further exploration. Recent studies have demonstrated that chaperonin­containing TCP1 subunit 6A (CCT6A) efficiently suppresses transforming growth factor­ß­mediated metastasis by inhibiting the function of SMAD family member 2 in lung cancer. However, the functional significance of CCT6A in other types of cancer, including BC, remains to be investigated. Therefore, this study evaluated CCT6A expression in BC samples, and further analysed its association with survival, clinicopathological parameters and related signalling pathways using online datasets. The present study indicated that CCT6A expression was significantly higher in BC tissues compared with in surrounding noncancerous tissues at both mRNA and protein levels. Furthermore, increased CCT6A expression was significantly associated with poor survival, including overall survival, relapse­free survival, distant metastasis­free survival and post progression survival, in patients with BC. Pathway finder analysis indicated that CCT6A was significantly associated with the cell cycle, and its expression was significantly positively correlated with cyclin (CCN)B2 and CCNA2 expression. Taken together, to the best of our knowledge, the present study is the first to indicate that CCT6A may serve a significant role in BC tumour progression.

Expression profiles analysis identifies the values of carcinogenesis and the prognostic prediction of three genes in adrenocortical carcinoma.

Adrenocortical carcinoma (ACC) is a rare disease associated with a poor prognosis. Furthermore, the underlying molecular mechanism of carcinogenesis is poorly understood, and prognostic prediction of ACC has low accuracy. In the present study, a bioinformatics approach was used to investigate the molecular mechanisms and prognosis of ACC. Samples of adrenal tumors were collected from patients undergoing adrenalectomy at the Department of Urology, the First Hospital of China Medical University. The analyzed gene datasets were downloaded from the Gene Expression Omnibus and The Cancer Genome Atlas (TCGA) database. Following this, the differentially expressed genes (DEGs) were included in Gene Ontology enrichment, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, protein­protein interaction network and survival analyses. MTT colorimetric assays, colony formation assays and 5­ethynyl­20­deoxyuridine incorporation assays were also conducted to evaluate ACC cell proliferation. The identified DEGs included 20 downregulated genes and 51 upregulated genes, which were highly associated with the cell cycle, organelle fission, chromosome segregation, cell division and spindle stability. The top 14 hub genes were subsequently confirmed by reverse transcription­quantitative polymerase chain reaction in ACC and adrenocortical adenoma samples. It was identified that the nuclear division cycle 80, cyclin B2 and topoisomerase 2­α may serve important roles in adrenocortical tumor development. Furthermore, these three genes predicted overall survival and recurrence­free survival in patients with ACC from the TCGA cohort. The findings identified three novel genes that have important roles in carcinogenesis and in the prognostic prediction of ACC.