Explore the vast range of titles available.

Circular RNAs (circRNAs) are recently identified new noncoding RNAs and play an important role in tumorigenesis. Previous studies have indicated that hsa_circRNA_102958 is a potential diagnostic indicator in gastric cancer. However, its role in colorectal cancer (CRC) is poorly understood. qRT-PCR and ISH were used to test gene expression in tissues. Survival rate was analzyed by Kaplan-Meier curve. Luciferase reporter assay was used to determine the interaction between circRNA and miRNA or between miRNA and mRNA. Western blotting was used to test protein expression. CCK8 and colony formation assay was used to analyze proliferation. Transwell assay was used for migration and invasion determination. In our research, we found that hsa_circRNA_102958 expression was significantly increased in CRC tissues, compared to adjacent normal controls. Increased hsa_circRNA_102958 levels in CRC patients indicated a poor prognosis. The effects of hsa_circRNA_102958 on CRC cell proliferation, migration and invasion were then determined by CCK8, colony formation and Transwell assays. We showed that hsa_circRNA_102958 silencing markedly suppressed CRC growth, migration and invasion. Furthermore, hsa_circRNA_102958 was identified as a sponge for miR-585. We demonstrated that hsa_circRNA_102958 promoted CDC25B expression through inhibiting miR-585 in CRC. Rescue assays illustrated that CDC25B overexpression reversed the suppressive effects of hsa_circRNA_102958 silencing on CRC. Taken together, our findings revealed the novel oncogenic roles of hsa_circRNA_102958 in CRC through miR-585/CDC25B axis.

Radiotherapy is commonly used to treat many cancers, and their sensitivity to radiation is crucial for favorable outcomes. This study investigated whether the immediate early response 5 (IER5) protein affects Cdc25B protein expression in HeLa cells after gamma irradiation. IER5 was knocked down using RNA interference (RNAi) in HeLa cells irradiated with 2 or 4 Gy of gamma rays. The mRNA and protein expression levels were subsequently determined via qRT–PCR and western blotting. The distribution of cells during the cell cycle was also determined using flow cytometry. IER5 protein levels were successfully reduced with RNAi. Variations in IER5 levels led to differences in Cdc25B mRNA and protein levels. Moreover, IER5 affected the proportion of cells in the G2 phase, which is regulated mainly by Cdc25B. Pearson correlation analysis was conducted on the expression levels of IER5 and Cdc25B in HeLa cells and the IER5‐silenced HeLa (siIER5‐HeLa) cell line at various time points after exposure to 4 Gy of gamma rays, and a negative correlation was detected between IER5 and Cdc25B expression levels, with correlation coefficients of −0.686 and −0.663, respectively. Additionally, variations in IER5 levels led to differences in the expression levels of p53, NF‐YB, and p300, which may be putative transcriptional regulators of Cdc25B. These results suggest that IER5 plays a negative role in regulating Cdc25B expression, which may involve interactions with the transcriptional regulators p53, NF‐YB, and p300.

Overexpression of nonmutated proteins involved in oncogenesis is a mechanism by which such proteins become immunogenic. We questioned whether overexpressed colorectal cancer associated proteins found at higher incidence and associated with poor prognosis could be effective vaccine antigens. We explored whether vaccines targeting these proteins could inhibit the development of intestinal tumors in the azoxymethane (AOM)-induced colon model and APC Min mice. Humoral immunity was evaluated by ELISA. Web-based algorithms identified putative Class II binding epitopes of the antigens. Peptide and protein specific T-cells were identified from human peripheral blood mononuclear cells using IFN-gamma ELISPOT. Peptides highly homologous between mouse and man were formulated into vaccines and tested for immunogenicity in mice and tumor challenge. Mice treated with AOM and APC Min transgenic mice were vaccinated and monitored for tumors. Serum IgG for CDC25B, COX2, RCAS1, and FASCIN1 was significantly elevated in colorectal cancer patient sera compared to volunteers (CDC25B p=0.002, COX-2 p=0.001, FASCIN1 and RCAS1 p<0.0001). Epitopes predicted to bind to human class II MHC were identified for each protein and T-cells specific for both the peptides and corresponding recombinant protein were generated from human lymphocytes validating these proteins as human antigens. Some peptides were highly homologous between mouse and humans and after immunization, mice developed both peptide and protein specific IFN-γ-secreting cell responses to CDC25B, COX2 and RCAS1, but not FASCIN1. FVB/nJ mice immunized with CDC25B or COX2 peptides showed significant inhibition of growth of the syngeneic MC38 tumor compared to control (p<0.0001). RCAS1 peptide vaccination showed no anti-tumor effect. In the prophylactic setting, after immunization with CDC25B or COX2 peptides mice treated with AOM developed significantly fewer tumors as compared to controls (p<0.0002) with 50% of mice remaining tumor free in each antigen group. APC Min mice immunized with CDC25B or COX2 peptides developed fewer small bowel tumors as compared to controls (p=0.01 and p=0.02 respectively). Immunization with CDC25B and COX2 epitopes consistently suppressed tumor development in each model evaluated. These data lay the foundation for the development of multi-antigen vaccines for the treatment and prevention of colorectal cancer.

Background CDC25B, as a member of the cell cycle regulating protein family, is located in the cytoplasm and is involved in the transition of the cell cycle and mitosis. CDC25B is highly expressed in various tumors and is a newly discovered oncogene. This study aimed to investigate the impact of CDC25B on mitoxantrone resistance in stomach adenocarcinoma (STAD) and its possible mechanisms. Methods This study analyzed the expression of CDC25B and its potential transcription factor E2F3 in STAD, as well as the IC 50 values of tumor tissues by bioinformatics analysis. Expression levels of CDC25B and E2F3 in STAD cells were measured by qRT-PCR. MTT was utilized to evaluate cell viability and IC 50 values of STAD cells, and comet assay was utilized to analyze the level of DNA damage in STAD cells. Western blot was used to analyze the expression of DNA damage-related proteins. The targeting relationship between E2F3 and CDC25B was validated by dual-luciferase and ChIP assays. Results Bioinformatics analysis and molecular experiments showed that CDC25B and E2F3 were highly expressed in STAD, and CDC25B was enriched in the mismatch repair and nucleotide excision repair pathways. The IC 50 values of tumor tissues with high expression of CDC25B were relatively high. Dual-luciferase and ChIP assays confirmed that CDC25B could be transcriptionally activated by E2F3. Cell experiments revealed that CDC25B promoted mitoxantrone resistance in STAD cells by regulating DNA damage. Further research found that low expression of E2F3 inhibited mitoxantrone resistance in STAD cells by DNA damage, but overexpression of CDC25B reversed the impact of E2F3 knockdown on mitoxantrone resistance in STAD cells. Conclusion This study confirmed a novel mechanism by which E2F3/CDC25B mediated DNA damage to promote mitoxantrone resistance in STAD cells, providing a new therapeutic target for STAD treatment.

The Aurora protein kinases are well-established regulators of spindle building and chromosome segregation in mitotic and meiotic cells. In mouse oocytes, there is significant Aurora kinase A (AURKA) compensatory abilities when the other Aurora kinase homologs are deleted. Whether the other homologs, AURKB or AURKC can compensate for loss of AURKA is not known. Using a conditional mouse oocyte knockout model, we demonstrate that this compensation is not reciprocal because female oocyte-specific knockout mice are sterile, and their oocytes fail to complete meiosis I. In determining AURKA-specific functions, we demonstrate that its first meiotic requirement is to activate Polo-like kinase 1 at acentriolar microtubule organizing centers (aMTOCs; meiotic spindle poles). This activation induces fragmentation of the aMTOCs, a step essential for building a bipolar spindle. We also show that AURKA is required for regulating localization of TACC3, another protein required for spindle building. We conclude that AURKA has multiple functions essential to completing MI that are distinct from AURKB and AURKC.

The cell cycle machinery controls cell proliferation and the dysregulation of the cell cycle lies at the heart of carcinogenesis. Thus, exploring the unknown regulators involved in the cell cycle not only contribute to better understanding of cell proliferation but also provide substantial improvement to cancer therapy. In this study, we identified that the expression of methyltransferase METTL3 was upregulated in the M phase. Overexpression of METTL3 facilitated cell cycle progression, induced cell proliferation in vitro and enhanced tumorigenicity in vivo, while knockdown of METTL3 reversed these processes. METTL3 induced CDC25B mRNA m6A modification in the M phase, which accelerated the translation of CDC25B mRNA through YTHDF1-dependent m6A modification. Clinical data analysis showed that METTL3 and CDC25B were highly expressed in cervical cancer. Our work reveals that a new mechanism regulates cell cycle progression through the METTL3/m6A/CDC25B pathway, which provides insight into the critical roles of m6A methylation in the cell cycle.

This study aimed to identify diagnostic gene biomarkers for colorectal cancer (CRC) by analyzing differentially expressed genes (DEGs) in tumor and adjacent normal samples across five colon cancer gene-expression profiles (GSE10950, GSE25070, GSE41328, GSE74602, GSE142279) from the Gene Expression Omnibus (GEO) database. Intersecting identified DEGs with the module with the highest correlation to gene expression patterns of tumor samples in the gene co-expression network analysis revealed 283 overlapped genes. Centrality measures were calculated for these genes in the reconstructed STRING protein–protein interaction network. Applying LASSO logistic regression, eleven genes were ultimately recognized as candidate diagnostic genes. Among these genes, the area under the receiver operating characteristic curve (AUROC) values for nine genes (CDC25B, CDK4, IQGAP3, MMP1, MMP7, SLC7A5, TEAD4, TRIB3, and UHRF1) surpassed the threshold of 0.92 in both the training and validation sets. We evaluated the diagnostic performance of these genes with four machine learning algorithms: random forest (RF), support vector machines (SVM), artificial neural network (ANN), and gradient boosting machine (GBM). In the testing dataset (GSE21815 and GSE106582), the AUROC scores were greater than 0.95 for all of the machine learning algorithms, indicating the high diagnostic performance of the nine genes. Besides, these nine genes are also significantly correlated to twelve immune cells, namely Mast cells activated, Macrophages M0, M1, and M2, Neutrophils, T cells CD4 memory activated, T cells follicular helper, T cells CD8, T cells CD4 memory resting, B cells memory, Plasma cells, and Mast cells resting (P < 0.05). These results strongly suggest that all of the nine genes have the potential to serve as reliable diagnostic biomarkers for CRC.

The subcortical maternal complex (SCMC) is essential for safeguarding female fertility in mammals. Assembled in oocytes, the SCMC maintains the cleavage of early embryos, but the underlying mechanism remains unclear. Here, we report that 14-3-3, a multifunctional protein, is a component of the SCMC. By resolving the structure of the 14-3-3-containing SCMC, we discover that phosphorylation of TLE6 contributes to the recruitment of 14-3-3. Mechanistically, during maternal-to-embryo transition, the SCMC stabilizes 14-3-3 protein and contributes to the proper control of CDC25B, thus ensuring the activation of the maturation-promoting factor and mitotic entry in mouse zygotes. Notably, the SCMC establishes a conserved molecular link with 14-3-3 and CDC25B in human oocytes/embryos. This study discloses the molecular mechanism through which the SCMC regulates the cell cycle in early embryos and elucidates the function of the SCMC in mammalian early embryogenesis. The subcortical maternal complex (SCMC) maintains cleavage of early embryos. Here the authors identify 14-3-3 as a component of the SCMC and show that phosphorylation of TLE6 contributes to 14-3-3 recruitment and stabilization, ensuring mitotic entry in mouse zygotes.

Circular RNAs (circRNAs) play a crucial role in gene expression regulation. CircHIPK3 is a circRNA derived from Exon 2 of HIPK3 gene and its role in prostate cancer (PCa) is still unclear. CCK8 assays, flow cytometry and colony formation assays were performed to assess the effects of circHIPK3 in PCa cells. Bioinformatics analysis, RNA pull-down assay, RNA immunoprecipitation assay (RIP), and luciferase activity assay were performed to dissect the mechanism underlying circHIPK3-mediated G2/M transition in PCa cells. CircHIPK3 expression was upregulated in PCa cells and prostate cancer tissues. Overexpression of circHIPK3 or circHIPK3 silencing altered PCa viability, proliferation and apoptosis in vitro. CircHIPK3 could sponge miR-338-3p and inhibit its activity, resulting in increased expression of Cdc25B and Cdc2 in vitro. CircHIPK3 promotes G2/M transition and induces PCa cell proliferation by sponging miR-338-3p and increasing the expression of Cdc25B and Cdc2. CircHIPK3 may play an oncogenic role in PCa.

Background N6-methyladenosine (m6A) RNA methylation and its methyltransferase METTL3 have been widely reported to be involved in different cancers by regulating RNA metabolism and function. Here, we aimed to explore the biological function and clinical significance of m6A modification and METTL3 in head and neck squamous cell carcinoma (HNSCC). Methods The prognostic value of METTL3 expression was evaluated using tissue microarray and immunohistochemical staining analyses in a human HNSCC cohort. The biological role and mechanism of METTL3 in HNSCC tumour growth, metastasis and angiogenesis were determined in vitro and in vivo. Results M6A levels and METTL3 expressions in HNSCC tissues were significantly increased compared with paired adjacent tissues. Meanwhile, METTL3 was an independent risk factor for the prognosis of HNSCC patients. Moreover, METTL3 overexpression promoted HNSCC cell proliferation, migration, invasion, and angiogenesis, while knockdown of METTL3 had an opposite effect in vivo and in vitro. Mechanistically, METTL3 enhanced the m6A modification of CDC25B mRNA, which maintained its stability and upregulated its expression, thereby activating G2/M phase of cell cycle and leading to HNSCC malignant progression. Conclusions METTL3 may be a potential prognostic biomarker and therapeutic target for HNSCC.