Expression Of CCNB1 Research Articles

Inorganic Polyphosphate Promotes Colorectal Cancer Growth via TRPM8 Receptor Signaling Pathway

Background: Colorectal cancer (CRC) is characterized by a pro-inflammatory microenvironment and features high-energy-supply molecules that assure tumor growth. A still less studied macromolecule is inorganic polyphosphate (iPolyP), a high-energy linear polymer that is ubiquitous in all forms of life. Made up of hundreds of repeated orthophosphate units, iPolyP is essential for a wide variety of functions in mammalian cells, including the regulation of proliferative signaling pathways. Some evidence has suggested its involvement in carcinogenesis, although more studies need to be pursued. Moreover, iPolyP regulates several homeostatic processes in animals, spanning from energy metabolism to blood coagulation and tissue regeneration. Results: In this study, we tested the role of iPolyP on CRC proliferation, using in vitro and ex vivo approaches, in order to evaluate its effect on tumor growth. We found that iPolyP is significantly increased in tumor tissues, derived from affected individuals enrolled in this study, compared to the corresponding peritumoral counterparts. In addition, iPolyP signaling occurs through the TRPM8 receptor, a well-characterized Na+ and Ca2+ ion channel often overexpressed in CRC and linked with poor prognosis, thus promoting CRC cell proliferation. The pharmacological inhibition of TRPM8 or RNA interference experiments performed in established CRC cell lines, such as Caco-2 and SW620, showed that the involvement of TRPM8 is essential, greater than that of the other two known iPolyP receptors, P2Y1 and RAGE. The presence of iPolyP drives cancer cells towards the mitotic phase of the cell cycle by enhancing the expression of ccnb1, which encodes the Cyclin B protein. In vitro 2D and 3D data reflected the ex vivo results, obtained by the generation of CRC-derived organoids, which increased in size. Conclusions: These results indicate that iPolyP may be considered a novel and unexpected early biomarker supporting colorectal cancer cell proliferation.

CtIP regulates G2/M transition and bipolar spindle assembly during mouse oocyte meiosis

CtBP-interacting protein (CtIP) is known for its multifaceted roles in DNA repair and genomic stability, directing the homologous recombination-mediated DNA double-stranded break (DSBs) repair pathway via DNA end resection, an essential error-free repair process vital for genome stability. Mammalian oocytes are highly prone to DNA damage accumulation due to prolonged G2/prophase arrest. Here, we explore the functions of CtIP in meiotic cell cycle regulation via a mouse oocyte model. Depletion of CtIP by siRNA injection results in delayed germinal vesicle breakdown and failed polar body extrusion. Mechanistically, CtIP deficiency increases DNA damage and decreases the expression and nuclear entry of CCNB1, resulting in marked impairment of meiotic resumption, which can be rescued by exogenous CCNB1 overexpression. Furthermore, depletion of CtIP disrupts MTOCs coalescence at spindle poles as indicated by failed accumulation of γ-tubulin, p-Aurora kinase A, Kif2A, and TPX2, leading to abnormal spindle assembly and prometaphase arrest. These results provide valuable insights into the important roles of CtIP in the G2/M checkpoint and spindle assembly in mouse oocyte meiotic cell cycle regulation.

DEPDC1B: A novel tumor suppressor gene associated with immune infiltration in colon adenocarcinoma.

Recent research indicates a positive correlation between DEP structural domain-containing 1B (DEPDC1B) and the cell cycle in various tumors. However, the role of DEPDC1B in the infiltration of the tumor immune microenvironment (TIME) remains unexplored. We analyzed the differential expression and prognostic significance of DEPDC1B in colon adenocarcinoma (COAD) using the R package "limma" and the Gene Expression Profiling Interactive Analysis (GEPIA) website. Gene set enrichment analysis (GSEA) was employed to investigate the functions and interactions of DEPDC1B expression in COAD. Cell Counting Kit-8 (CCK-8) assays and colony formation assays were utilized to assess the proliferative function of DEPDC1B. Correlations between DEPDC1B expression and tumor-infiltrating immune cells, immune checkpoints, tumor mutational burden (TMB), and microsatellite instability (MSI) status were examined using Spearman correlation analysis and CIBERSORT. DEPDC1B was highly expressed in COAD. Elevated DEPDC1B expression was associated with lower epithelial-to-mesenchymal transition (EMT) and TNM stages, leading to a favorable prognosis. DEPDC1B mRNA was prominently expressed in COAD cell lines. CCK-8 and colony formation assays demonstrated that DEPDC1B inhibited the proliferation of COAD cells. Analysis using the CIBERSORT database and Spearman correlation revealed that DEPDC1B correlated with four types of tumor-infiltrating immune cells. Furthermore, high DEPDC1B expression was linked to the expression of PD-L1, CTLA4, SIGLEC15, PD-L2, TMB, and MSI-H. High DEPDC1B expression also indicated responsiveness to anti-PD-L1 immunotherapy. DEPDC1B inhibits the proliferation of COAD cells and positively regulates the cell cycle, showing a positive correlation with CCNB1 and PBK expression. DEPDC1B expression in COAD is associated with tumor-infiltrating immune cells, immune checkpoints, TMB, and MSI-H in the tumor immune microenvironment. This suggests that DEPDC1B may serve as a novel prognostic marker and a potential target for immunotherapy in COAD.

Ring Finger Protein 217 Inhibits Ovarian Cancer Progression by Down‐Regulating HAX1 Expression

AbstractRing finger protein 217 (RNF217) has been found to interact with the antiapoptotic protein HS‐1‐associated protein X‐1 (HAX‐1) in myeloid leukemia cells. However, the understanding of RNF217 in ovarian cancer progression remains limited. The relative expression of RNF217 is screened in ovarian cancer using the GEPIA database and calculated its correlation with MKI67, CCNB1, and CDK4. OVCAR‐3 and SK‐OV‐3 cells are transfected with RNF217‐overexpression plasmids. Cell‐counting kit‐8 assay is utilized to assess proliferation. Immunoprecipitation is performed to reveal the interaction between RNF217 and HAX‐1, and a cycloheximide chase assay is performed to analyze HAX‐1 degradation. The GEPIA database indicated down‐regulated expression of RNF217 in ovarian cancer, negatively correlated with MKI67 (R = ‐0.26, P = 1.8e‐09), CCNB1 (R = ‐0.37, P = 3.2e‐18), and CDK4 expression (R = ‐0.24, P = 3.4e‐08). RNF217 overexpression down‐regulated the relative expression of MKI67, CCNB1, and CDK4 in OVCAR‐3 and SK‐OV‐3 cells, resulting in diminished proliferation. In vivo studies using OVCAR‐3 and SK‐OV‐3 cell line‐derived xenograft models also showed that RNF217 overexpression reduced ovarian cancer volume and weight. Furthermore, RNF217 overexpression in SK‐OV‐3 cells inhibited the protein expression of HAX1 by reducing its stability. In conclusion, RNF217 inhibits ovarian cancer progression by down‐regulating HS‐1‐associated protein X‐1 expression.

The molecular mechanism underlying KRAS regulation on STK31 expression in pancreatic ductal adenocarcinoma.

KRAS gene mutations are common in pancreatic ductal adenocarcinoma (PDAC), but targeting mutant KRAS is still challenging. Here, an endoribonuclease-prepared small interfering RNA (esiRNA) library was used to screen new kinases that play critical roles in PDAC driven by KRAS gene mutations, and serine/threonine kinase 31 (STK31) was identified and characterized as a potential therapeutic target for KRAS-mutant PDAC. Our results showed that STK31 was upregulated in KRAS-mutant PDAC patients with poor survival and highly expressed in PDAC cell lines with KRASG12D mutation. Inhibition of STK31 in KRAS-mutant cell lines significantly reduced PDAC cell growth invitro and hindered tumor growth invivo. Gain and loss of function experiments revealed that STK31 is a downstream target of KRAS in PDAC. A pharmacological inhibition assay showed MAPK/ERK signaling involved in STK31 regulation. The further mechanistic study validated that c-Jun, regulated by KRAS/MAPK signaling, directly modulates the transcription level of STK31 by binding to its promoter region. Through RNA sequencing, we found that the cell cycle regulators CCNB1 and CDC25C are downstream targets of STK31. Taken together, our results indicate that STK31, which is the downstream target of the KRAS/MAPK/ERK/c-Jun signaling pathway in KRAS-mutant PDAC, promotes PDAC cell growth by modulating the expression of the cell cycle regulators CCNB1 and CDC25C.

Baitouweng decoction suppresses growth of esophageal carcinoma cells through miR-495-3p/BUB1/STAT3 axis.

Esophageal carcinoma (EC) is one of the most prevalent cancers in human populations worldwide. Baitouweng decoction is one of the most important Chinese medicine formulas, with the potential to treat cancer. To investigate the role and mechanism of Baitouweng decoction on EC cells. Differentially expressed genes (DEGs) in EC tissues and normal tissues were screened by the cDNA microarray technique and by bioinformatics methods. The target genes of microRNAs were predicted based on the TargetScan database and verified by dual luciferase gene reporter assay. We used Baitouweng decoction to intervene EC cells, and detected the activity of EC9706 and KYSE150 cells by the MTT method. Cell cycle and apoptosis were measured by flow cytometry. The expression of BUB1 mRNA and miR-495-3p was measured by qRT-PCR. The protein levels of BUB1, STAT3, p-STAT3, CCNB1, CDK1, Bax, Caspase3, and Caspase9 were measured by Western blot analysis. The migration and invasion abilities of the cells were measured by wound-healing assay and Transwell invasion assay, respectively. DEGs identified are involved in biological processes, signaling pathways, and network construction, which are mainly related to mitosis. BUB1 was the key hub gene, and it is also a target gene of miR-495-3p. Baitouweng decoction could upregulate miR-495-3p and inhibit BUB1 expression. In vitro experiments showed that Baitouweng decoction significantly inhibited the migration and invasion of EC cells and induced apoptosis and G2/M phase arrest. After treatment with Baitouweng decoction, the expression of Bax, Caspase 3, and Caspase 9 in EC cells increased significantly, while the expression of BUB1, CCNB1, and CDK1 decreased significantly. Moreover, the STAT3 signaling pathway may play an important role in this process. Baitouweng decoction has a significant inhibitory effect on EC cell growth. BUB1 is a potential therapeutic target for EC. Further analysis showed that Baitouweng decoction may inhibit the growth of EC cells by upregulating miR-495-3p targeting the BUB1-mediated STAT3 signal pathway.

Marine algae-derived oligosaccharide via protein crotonylation of key targeting for management of type 2 diabetes mellitus in the elderly

Global aging is a tendency of the world, as is the increasing prevalence of diabetes, and the two are closely linked. In our early research, Enteromorpha prolifera oligosaccharide (EPO) possesses the excellent ability of anti-oxidative, anti-inflammatory, and anti-diabetic. We aim to further explore the deeper mechanism of how EPO delays aging and regulates glycometabolism. EPO effectively impacts crotonylation procession to enhance glucose metabolism and reduce cell senescence in aging diabetic rats. Crotonylation modification of XPO1 influences the expression of critical genes, including p53, CDK1, and CCNB1, which affect cell cycle regulation and aging. Additionally, EPO improves glucose metabolism by inhibiting the crotonylation modification of HSPA8-K126 and activating the AKT pathway. EPO promotes crotonylation of histones in intestinal cells, influencing the aging process by increasing the butyric acid-producing bacteria Ruminococcaceae. The observed enhancement in pyrimidine metabolism underscores EPO’s potential role in regulating intestinal health, presenting a promising avenue for delaying aging. In summary, our findings affirm EPO as a naturally bioactive ingredient with significant potential for anti-aging and antidiabetic interventions.

Study on the mechanism of quercetin in Sini Decoction Plus Ginseng Soup to inhibit liver cancer and HBV virus replication through CDK1.

To explore the anti-tumor and anti-virus key active ingredients of Sini Decoction Plus Ginseng Soup (SNRS) and their mechanisms. The main ingredients of SNRS were analyzed by network pharmacology, and quercetin was identified as the key active ingredient. Then, we obtained the targets of quercetin by using Drugbank, PharmMapper, and SwissTargetPrediction databases. Then, the targets of HBV-related hepatocellular carcinoma (HBV-related HCC) were obtained by using Genecards database. In addition, using the gene expression profiles of HBV-related HCC patients in GEO database and the genes with the greatest survival difference in GEPIA 2 database identified the potential targets of quercetin. In addition, the mechanism of potential genes was studied through GO, KEGG analysis, and PPI network. Using AUC and survival analysis to evaluate the diagnostic and prognostic value of cyclin-dependent kinase 1 (CDK1) and CCNB1. Finally, the effects of quercetin on proliferation of Hep3B and HepG2215 cells and the level of CDK1 and CCNB1 were verified invitro. ELISA was used to measure the expression levels of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) after the intervention by quercetin for 24 h and 48 h in HepG2215 cell. The first 10 key ingredients of SNRS were identified, and quercetin was the most key ingredient. The 101 potential quercetin targets were identified for the treatment of HBV-related HCC. GO and KEGG showed that 101 potential target enrichment in cancer and cell cycle regulation. By Venn analysis, CDK1 and CCNB1 were intersection targets, which could be used as potential targets for the action of quercetin on HBV-related HCC. Moreover, the expression of CDK1 and CCNB1 was highly expressed in the high-risk group, while the OS rate was low. The 1-year, 3-year and 5-year area under the curve (AUC) curves of CDK1 and CCNB1 were 0.724, 0.676, 0.622 and 0.745, 0.678, 0.634, respectively. Moreover, experimental results also showed that quercetin inhibited cell proliferation and reduced CDK1 expression in Hep3B and HepG2215 cells. The expressions of HBsAg and HBeAg in HepG2215 cell supernatant and cell gradually decreased with the increase of intervention time of quercetin and CDK1 inhibitor. Quercetin is a key ingredient of anti-HBV-related HCC activity and inhibits HBV replication in SNRS by inhibiting CDK1.

Regulatory Role of Meox1 in Muscle Growth of Sebastes schlegelii.

Meox1 is a critical transcription factor that plays a pivotal role in embryogenesis and muscle development. It has been established as a marker gene for growth-specific muscle stem cells in zebrafish. In this study, we identified the SsMeox1 gene in a large teleost fish, Sebastes schlegelii. Through in situ hybridization and histological analysis, we discovered that SsMeox1 can be employed as a specific marker of growth-specific muscle stem cells, which originate from the somite stage and are primarily situated in the external cell layer (ECL) and myosepta, with a minor population distributed among muscle fibers. The knockdown of SsMeox1 resulted in a significant increase in Ccnb1 expression, subsequently promoting cell cycle progression and potentially accelerating the depletion of the stem cell pool, which ultimately led to significant growth retardation. These findings suggest that SsMeox1 arrests the cell cycle of growth-specific muscle stem cells in the G2 phase by suppressing Ccnb1 expression, which is essential for maintaining the stability of the growth-specific muscle stem cell pool. Our study provides significant insights into the molecular mechanisms underlying the indeterminate growth of large teleosts.

Antiproliferative Activity of N-Acylhydrazone Derivative on Hepatocellular Carcinoma Cells Involves Transcriptional Regulation of Genes Required for G2/M Transition.

Liver cancer is the second leading cause of cancer-related death in males. It is estimated that approximately one million deaths will occur by 2030 due to hepatic cancer. Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer subtype and is commonly diagnosed at an advanced stage. The drug arsenal used in systemic therapy for HCC is very limited. Multikinase inhibitors sorafenib (Nexavar®) and lenvatinib (Lenvima®) have been used as first-line drugs with modest therapeutic effects. In this scenario, it is imperative to search for new therapeutic strategies for HCC. Herein, the antiproliferative activity of N-acylhydrazone derivatives was evaluated on HCC cells (HepG2 and Hep3B), which were chemically planned on the ALL-993 scaffold, a potent inhibitor of vascular endothelial growth factor 2 (VEGFR2). The substances efficiently reduced the viability of HCC cells, and the LASSBio-2052 derivative was the most effective. Further, we demonstrated that LASSBio-2052 treatment induced FOXM1 downregulation, which compromises the transcriptional activation of genes required for G2/M transition, such as AURKA and AURKB, PLK1, and CDK1. In addition, LASSBio-2052 significantly reduced CCNB1 and CCND1 expression in HCC cells. Our findings indicate that LASSBio-2052 is a promising prototype for further in vivo studies.

Cyclin B1: A potential prognostic and immunological biomarker in pan-cancer.

Cyclin B1 (CCNB1) encodes a regulatory protein essential for the regulation of cell mitosis, particularly in controlling the G2/M transition phase of the cell cycle. Current research has implicated CCNB1 in the progression of various types of cancer, including gastric cancer, breast cancer, and non-small cell lung cancer. In this study, we conducted a pan-cancer analysis of CCNB1 to investigate its prognostic significance and immunological aspects. Our comprehensive investigation covered a wide range of analyses, including gene expression, promoter methylation, genetic alterations, immune infiltration, immune regulators, and enrichment studies. We utilized multiple databases and tools for this purpose, such as The Cancer Genome Atlas (TCGA), the Genotype-Tissue Expression (GTEx) project, the Human Protein Atlas (HPA), the University of Alabama at Birmingham CANcer data analysis Portal (UALCAN), the Gene Expression Profiling Interactive Analysis (GEPIA), the DNA Methylation Interactive Visualization Database (DNMIVD), the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), Sangerbox, and cBioPortal. Data analyses were executed using GraphPad Prism software, R software, and various online tools. Our findings demonstrated a significant increase in CCNB1 expression across 28 cancer types. Elevated CCNB1 expression correlated with decreased overall survival (OS) in 11 cancer types and disease-free survival (DFS) in 12 cancer types. Additionally, DNA promoter methylation levels were significantly decreased in 14 cancer types. Furthermore, the study verified a significant association between CCNB1 expression and immune infiltration, immune modulators, microsatellite instability (MSI), and tumor mutational burden (TMB). Enrichment analysis indicated that CCNB1 is involved in multiple cellular pathways. Collectively, our results suggested that CCNB1 has the potential to serve as a valuable prognostic biomarker and may be a promising target for immunotherapy in various cancer types.

Transcriptomic analysis reveals the inhibitory effect of beta-sitosterol on proliferation of bovine preadipocytes

Fat deposition affects beef quantity and quality via preadipocyte proliferation. Beta-sitosterol, a natural small molecular compound, has various functions, such as anti-inflammation, antibacterial, and anticancer properties. The mechanism of action of Beta-sitosterol on bovine preadipocytes remains unclear. This study, based on RNA-seq, reveals the impact of Beta -sitosterol on the proliferation of bovine preadipocytes. Compared to the control group, Beta-sitosterol demonstrated a more pronounced inhibitory effect on cell proliferation after 48 hours of treatment than after 24 hours, as evidenced by the results of EdU staining and flow cytometry. RNA-seq and Western Blot analyses further substantiated these findings. Our results suggest that the impact of Beta-sitosterol on the proliferation of bovine preadipocytes is not significant after a 24-hour treatment. It is only after extending the treatment time to 48 hours that Beta-sitosterol may induce cell cycle arrest at the G2/M phase by suppressing the expression of CCNB1, thereby inhibiting the proliferation of bovine preadipocytes.

AURKA promotes renal cell carcinoma progression via regulation of CCNB1 transcription

AURKA is a member of the serine/threonine kinase family and its kinase activity is crucial for the progression of mitosis. Recent studies have highlighted the therapeutic significance of AURKA inhibition in multiple cancer types. However, the specific mechanisms by which AURKA contributes to the progression of renal cell carcinoma (RCC) have not been fully elucidated. In this study, AURKA expression level was identified in human RCC tissues by immunohistochemical (IHC) staining. The function of AURKA on cell malignant phenotypes was evaluated in vitro after AURKA inhibition. The subcutaneous xenograft was conducted to confirm the in vivo effect of AURKA knockdown on growth of RCC cells. Finally, Co-IP, luciferase assay and ChIP experiments were performed to reveal the regulatory mechanism of AURKA on CCNB1. Our results showed a significant upregulation of AURKA in RCC tissues and cell lines, and a high AURKA expression was associated with poor prognosis. AURKA knockdown inhibited RCC cell proliferation and migration, induced cell apoptosis, and led to G1/G2 phase arrest. This effect was further confirmed by the use of an AURKA inhibitor. Mechanistically, AURKA interacted with E2F1, and subsequently recruited it to the promoter region of CCNB1. CCNB1 expression was essential for AURKA-induced RCC progression. Collectively, our results suggested that AURKA plays an important role in development of RCC via regulating CCNB1 transcription.

Bioinformatics analysis highlights CCNB1 as a potential prognostic biomarker and an anti-kidney renal papillary cell carcinoma drug target.

Kidney renal papillary cell carcinoma (KIRP) is a common urinary tumor that causes lymph node invasion. Once metastatic, the prognosis is poor and there is a lack of effective early diagnostic markers for this tumor. The expression of CCNB1 in KIRP tumor tissues was significantly higher than that in normal tissues in The Cancer Genome Atlas database with or without the genotype-tissue expression database, and a consistent result was obtained in 32 paired tissues. In addition, CCNB1 expression increased remarkably with the progression of the T and M stages. Moreover, using the online HPA database, we verified that the immunohistochemical scores of CCNB1 in KIRP were higher than those in the normal kidney tissues. The higher expression group of CCNB1 showed a worse prognosis in KIRP. Moreover, the receiver operating characteristic curve, univariate and multivariate analyses, and construction of the column diagram further illustrated that CCNB1 was an independent prognostic factor for KIRP. Meanwhile, CCNB1 could better predict the 1- and 3-year survival rates of KIRP. Six genes were significantly and positively co-expressed with CCNB1. We also found that the CCNB1 high-expression group was enriched in the ECM_RECEPTOR_INTERACTION and FOCAL_ADHESION pathways. Finally, drug sensitivity analysis combined with molecular docking identified 5 targeting drugs with the strongest binding activity to CCNB1. CCNB1 is a potential and reliable biomarker for KIRP diagnosis and can be used to predict the survival of patients with KIRP. The 5 selected drugs targeting CCNB1 may provide new hopes for patients with KIRP metastasis.

Explore Key Genes and Mechanisms Involved in Colon Cancer Progression Based on Bioinformatics Analysis.

To explore underlying mechanisms related to the progression of colon cancer and identify hub genes associated with the prognosis of patients with colon cancer. GSE10950 and GSE62932 were downloaded from the Gene Expression Omnibus (GEO) database. GEO2R was utilized to screen out the differentially expressed genes (DEGs). Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted on DEGs. Moreover, STRING and Cytoscape software were utilized for establishing the network of protein-protein interaction (PPI) and identifying hub genes. Afterward, data from The Cancer Genome Atlas (TCGA) was utilized for identifying prognosis-related hub genes by Kaplan-Meier survival analysis. Colon cancer cell line LOVO and human normal intestinal epithelial cell line NCM-460 were exploited to demonstrate the differential expression of selected hub genes through RT-qPCR and western blot. The LOVO cells were transfected to regulate expressions of prognosis-associated genes, followed by exploring the effects of those genes on prognosis by Cell Counting Kit-8 assay and colony-forming assay for cancer cell proliferation, cell scratch test and transwell migration assay for cancer cell migration and Annexin V-PE/7-AAD double staining as well as flow cytometry for cancer cell apoptosis. In this study, 266 common DEGs were obtained from the intersection of two datasets. The GO analysis suggested the common DEGs mainly participated in the one-carbon metabolic process, cell cycle G2/M phase transition, organelle fission, cell cycle phase transition regulation, and regulation of mitotic cell cycle phase transition. The KEGG analysis demonstrated the common DEGs were related to the p53 signaling pathway, nitrogen metabolism, mineral absorption, and cell cycle. 10 hub genes including CCNB1, KIF4A, TPX2, MT1F, PRC1, PLK4, CALD1, MMP9, CLCA1, and MMP1 were identified and CCNB1, CLCA1, and PLK4 were prognosis-related. Increased expression of CCNB1, CLCA1, and PLK4 restrained proliferation as well as migration of cancer cells and induced apoptosis of cancer cells. CCNB1, KIF4A, TPX2, MT1F, PRC1, PLK4, CALD1, MMP9, CLCA1, and MMP1 were identified as hub genes and CCNB1, CLCA1, and PLK4 could inhibit the progression of colon cancer through inhibiting proliferation as well as migration of the cancer cell and promoting apoptosis of cancer cell.

Catalase expression is an independent prognostic marker in liver hepatocellular carcinoma

Abstract Objectives Liver hepatocellular carcinoma (LIHC) is the most common type of primary liver cancer and originates from hepatocytes, the main functional cells of the liver. It is a serious and aggressive cancer with a generally poor prognosis, especially when diagnosed at advanced stages. Reactive oxygen species (ROS) have been detected in LIHC and are involved in carcinogenesis and tumor progression. Here, a comprehensive analysis was performed to evaluate the effects of ROS-related genes on the prognosis of LIHC. Methods Using bioinformatical tools including Gene Expression Profiling Interactive Analysis (GEPIA2) and Q-omics, a comprehensive analysis was performed to evaluate the effects of ROS-related genes, including superoxide dismutases (SODs), glutathione peroxidases (GPXs), peroxiredoxins (PRDXs) and catalase (CAT) on the prognosis of LIHC using The Cancer Genome Atlas (TCGA) dataset and identified the most appropriate candidate genes. Then we further explored their effects on LIHC cell proliferation and drug selection for LIHC treatment. Results We found that CAT expression was significantly downregulated in late stage’s LIHC tissues compared to normal liver or early stage’s LIHC tissues, and high CAT expression was correlated with a favorable survival prognosis in LIHC. The expression of the CAT gene was associated with an inhibition of the “cell cycle” pathway. HepG2 and Hep3B cells’ growth was increased with a decrease in CAT expression by silencing its mRNA. As silencing of CAT in HepG2 and Hep3B cells, and its association with an increase in the expression of PLK1, CCNB1, CDC20, and PTTG1. A comparative 426 drug response in LIHC cells with different CAT expression, SU11274, a Met inhibitor, could serve as a therapeutic option when CAT levels are low in LIHC cells. Conclusions Our findings revealed that Met inhibitors could potentially control tumor progression and be used as a therapeutic option against LIHC with low CAT.

CircPVT1 Inhibits the Proliferation and Aids in Prediction of the Prognosis of Bladder Cancer.

Circular RNA PVT1 (circPVT1) is aberrantly expressed in several cancers, but its functional role and clinical relevance in bladder urothelial carcinoma (BLCA) remain unknown. This study aimed to identify the expression level of circPVT1 in BLCA and investigated its functional relevance with BLCA progression both in vitro and in vivo. GEPIA, UALCAN, and OncoLnc were referred to presented data. Quantitative real-time PCR (qPCR) was used for the measurement of transnational expression of genes in BLCA specimens and cell lines. Immunohistochemistry (IHC) and fluorescence in situ hybridization analysis (FISH) assays were performedto detect HER2 amplification, Pearson's correlation analysis to analyze the correlation between circPVT1 expression and clinical characteristics, Cox regression and K-M survival analyses to analyze prognostic factors. A nomogram was constructed for predicting prognosis. The proliferation of cells was measured by CCK-8 and colony formation assay, and the proliferation in vivo was evaluated using nude mouse models. qPCR was used to detect the expression of proliferation-related genes. circPVT1 was but mRNA PVT1 was not significantly overexpressed in BLCA. A high circPVT1 expression was associated with a better survival and negative HER2, but not with age, gender, and T stage. circPVT1 was an independent prognostic factor for the overall survival of BLCA patients. Knocking down circPVT1 promoted BLCA proliferation in vitro and in vivo. Knocking down circPVT1 upregulated ERBB2, MKI67, and PCNA expression and downregulated TP53 expression, but exerted no influence on CCND1 and CCNB1 expression. circPVT1 is a tumor suppressor and novel prognostic biomarker for BLCA.

Puerarin modulation of CENPA affects downstream PLK1 and CCNB1 expression to inhibit bladder cancer cell proliferation

Puerarin modulation of CENPA affects downstream PLK1 and CCNB1 expression to inhibit bladder cancer cell proliferation

Investigating the pharmacological mechanism of Zhengyuan jiaonang for treating colorectal cancer via network pharmacology analysis and experimental verification

Ethnopharmacological relevanceZhengyuan jiaonang (ZYJN) is a traditional Chinese patent medicine (CPM) used in China for adjuvant cancer therapy, which has been proved to have anti-fatigue effects. Aim of studyThe study aims to investigate the antitumor effects of ZYJN and its underlying mechanisms using subcutaneous transplant CT26 model. Materials and methodsFingerprint analysis of ZYJN was performed using high performance liquid chromatography. The potential targets of ZYJN were predicted using bioinformatic analysis, which were further validated by Western Blot assay. Subcutaneous transplant CT26 model was used to evaluate the antitumor effects of ZYJN. The effects of ZYJN on the tumor immune microenvironment were investigated by flow cytometry. Transparent imaging was used to investigate the effects of ZYJN on fibrosis and angiogenesis. ResultsZYJN could inhibit colorectal cancer growth when administered alone or in combination with 5-FU. The combination of ZYJN and 5-FU could significantly increase the serum level of albumin (ALB) and decrease the serum level of aspartate aminotransferase (AST). In addition, the combination of ZYJN at 0.75 g/kg and 5-FU significantly decreased the serum level of vascular endothelial growth factors (VEGF) and inhibited the angiogenesis of CT26 cancer. The combination of ZYJN at 1.50 g/kg and 5-FU could promote the fibrosis process of CT26 cancer. Additionally, combination of ZYJN and 5-FU could significantly increase the percentage of tumor-infiltrating T cells and CD4+ T cells in the late stage of CT26 model, while ZYJN at 1.50 g/kg increased the percentage of NK cells as well as CD8+ T cells in the early stage of CT26 model. Western Blot analysis revealed that administration of ZYJN at 0.75 g/kg reduced the expression of PI3K-p110α, CDK1, CCNB1 and MMP-9, and inhibited the phosphorylation of Akt (Thr308). ConclusionsZYJN could inhibit the tumor growth of CT26 colorectal cancer by promoting tumor fibrosis, suppressing angiogenesis, migration, and invasion and modulating the tumor immune microenvironment. ZYJN enhanced the efficacy and reduced the toxicity of chemotherapy drugs in combination therapy. Our findings provide evidence for the clinical application of ZYJN in cancer treatment.

Clinical and Molecular Characteristics of Gonadotroph Pituitary Tumors According to the WHO Classification

Since 2017, hormone-negative pituitary neuroendocrine tumors expressing the steroidogenic factor SF1 have been recognized as gonadotroph tumors (GnPT) but have been poorly studied. To further characterize their bio-clinical spectrum, 54 GnPT defined by immunostaining for FSH and/or LH (group 1, n = 41) or SF1 only (group 2, n = 13) were compared and studied for SF1, βFSH, βLH, CCNA2, CCNB1, CCND1, caspase 3, D2R, and AIP gene expression by qRT-PCR. Immunohistochemistry for AIP and/or D2R was performed in representative cases. Overall, patients were significantly younger in group 1 (P = 0.040 vs group 2), with a similar trend excluding recurrent cases (P = 0.078), and no significant difference in gender, tumor size, invasion or Ki67. SF1 expression was similar in both groups but negatively correlated with the patient’s age (P = 0.013) and positively correlated with βLH (P < 0.001) expression. Beta-FSH and AIP were significantly higher in group 1 (P = 0.042 and P = 0.024, respectively). Ki67 was unrelated to gonadotroph markers but positively correlated with CCNB1 (P = 0.001) and negatively correlated with CCND1 (P = 0.008). D2R and AIP were strongly correlated with each other (P < 0.001), and both positively correlated with SF1, βFSH, βLH, and CCND1. AIP immunopositivity was frequently observed in both groups, with a similar median score, and unrelated to Ki67. D2R immunostaining was best detected with a polyclonal antibody and mostly cytoplasmic. This study indicates that hormone-negative GnPT tend to occur in older patients but do not significantly differ from other GnPT in terms of invasion or proliferation. It also points out the current limits of D2R immunostaining in such tumors.