scholarly journals Coiled-Coil Domain Containing 80 Suppresses Nonylphenol-Induced Colorectal Cancer Cell Proliferation by Inhibiting the Activation of ERK1/2

2021 ◽  
Vol 9 ◽  
Author(s):  
Jing Wang ◽  
Yuan-wei Zhang ◽  
Nian-jie Zhang ◽  
Shuo Yin ◽  
Du-ji Ruan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Cell Growth ◽  
Differentially Expressed Genes ◽  
Endocrine Disrupting Chemicals ◽  
Coiled Coil ◽  
Underlying Mechanism ◽  
Differentially Expressed ◽  
Coiled Coil Domain ◽  
Upregulated Genes

Recently, the effect of endocrine-disrupting chemicals on the cancer procession has been a concern. Nonylphenol (NP) is a common environmental estrogen that has been shown to enhance the proliferation of colorectal cancer (CRC) cells in our previous studies; however, the underlying mechanism remains unclear. In this study, we confirmed the increased concentration of NP in the serum of patients with CRC. RNA sequencing was used to explore the differentially expressed genes after NP exposure. We found 16 upregulated genes and 12 downregulated genes in COLO205 cells after NP treatment. Among these differentially expressed genes, we found that coiled-coil domain containing 80 (CCDC80) was downregulated by NP treatment and was associated with CRC progression. Further experiments revealed that the overexpression of CCDC80 significantly suppressed NP-induced cell proliferation and recovered the reduced cell apoptosis. Meanwhile, the overexpression of CCDC80 significantly inhibited the activation of ERK1/2 induced by NP treatment. ERK1/2 inhibitor (PD98059) treatment also suppressed NP-induced CRC cell growth, but the overexpression of CCDC80 did not enhance the effect of ERK1/2 inhibitor. Taken together, NP treatment significantly inhibited the expression of CCDC80, and the overexpression of CCDC80 suppressed NP-induced CRC cell growth by inhibiting the activation of ERK1/2. These results suggest that NP could induce CRC cell growth by influencing the expression of multiple genes. CCDC80 and ERK1/2 inhibitors may be suitable therapeutic targets in NP-related CRC progression.

scholarly journals Identification of differentially expressed genes between mucinous adenocarcinoma and other adenocarcinoma of colorectal cancer using bioinformatics analysis

2020 ◽  
Vol 48 (8) ◽  
pp. 030006052094903
Author(s):  
Xue Zhang ◽  
Jing Zuo ◽  
Long Wang ◽  
Jing Han ◽  
Li Feng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Differentially Expressed Genes ◽  
Mucinous Adenocarcinoma ◽  
Wnt Signaling Pathway ◽  
Interaction Network ◽  
Differentially Expressed ◽  
Venn Diagram ◽  
Bicarbonate Transport ◽  
Hub Genes

Objective As a unique histological subtype of colorectal cancer (CRC), mucinous adenocarcinoma (MC) has a poor prognosis and responds poorly to treatment. Genes and markers related to MC have not been reported. Methods To identify biomarkers involved in development of MC compared with other common adenocarcinoma (AC) subtypes, four datasets were obtained from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified using GEO2R. A protein–protein interaction network was constructed. Functional annotation for DEGs was performed via DAVID, Metascape, and BiNGO. Significant modules and hub genes were identified using Cytoscape, and expression of hub genes and relationships between hub genes and MC were analyzed. Results The DEGs were mainly enriched in negative regulation of cell proliferation, bicarbonate transport, response to peptide hormone, cell–cell signaling, cell proliferation, and positive regulation of the canonical Wnt signaling pathway. The Venn diagram revealed eight significant hub genes: CXCL9, IDO1, MET, SNAI2, and ZEB2 were highly expressed in MC compared with AC, whereas AREG, TWIST1, and ZEB1 were expressed at a low level. AREG and MET might be significant biomarkers for MC. Conclusion The identified DEGs might help elucidate the pathogenesis of MC, identify potential targets, and improve treatment for CRC.

Identification of aberrantly methylated differentially expressed genes in melanoma

2020 ◽  
Author(s):  
Wei Han ◽  
Guo-liang Shen
Keyword(s):  
Gene Expression ◽  
Cell Proliferation ◽  
Differentially Expressed Genes ◽  
Enrichment Analysis ◽  
Differentially Expressed ◽  
Regulation Of Transcription ◽  
Biological Processes ◽  
Hub Genes ◽  
Positive Regulation ◽  
Upregulated Genes

Abstract Background: Skin Cutaneous Melanoma (SKCM) is known as an aggressive malignant cancer, which could be directly derived from melanocytic nevi. However, the molecular mechanisms underlying malignant transformation of melanocytes and melanoma tumor progression still remain unclear. Increasing researches showed significant roles of epigenetic modifications, especially DNA methylation, in melanoma. This study focused on identification and analysis of methylation-regulated differentially expressed genes (MeDEGs) between melanocytic nevus and malignant melanoma in genome-wide profiles. Methods: The gene expression profiling datasets (GSE3189 and GSE114445) and gene methylation profiling datasets (GSE86355 and GSE120878) were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) and differentially methylated genes (DMGs) were identified via GEO2R. MeDEGs were obtained by integrating the DEGs and DMGs. Then, functional enrichment analysis of MeDEGs were performed. STRING and Cytoscape were used to describe protein-protein interaction(PPI) network. Furthermore, survival analysis was implemented to select the prognostic hub genes. Finally, we conducted gene set enrichment analysis (GSEA) of hub genes. Results: We identified 237 hypomethylated, upregulated genes and 182 hypermethylated, downregulated genes. Hypomethylation-upregulated genes were enriched in biological processes of the oxidation-reduction process, cell proliferation, cell division, phosphorylation, extracellular matrix disassembly and protein sumoylation. Pathway enrichment showed selenocompound metabolism, small cell lung cancer and lysosome. Hypermethylation-downregulated genes were enriched in biological processes of positive regulation of transcription from RNA polymerase II promoter, cell adhesion, cell proliferation, positive regulation of transcription, DNA-templated and angiogenesis. The most significantly enriched pathways involved the transcriptional misregulation in cancer, circadian rhythm, tight junction, protein digestion and absorption and Hippo signaling pathway. After PPI establishment and survival analysis, seven prognostic hub genes were CKS2, DTL, KIF2C, KPNA2, MYBL2, TPX2 and FBL. Moreover, the most involved hallmarks obtained by GSEA were E2F targets, G2M checkpoint and mitotic spindle. Conclusions: Our study identified potential aberrantly methylated-differentially expressed genes participating in the process of malignant transformation from nevus to melanoma tissues based on comprehensive genomic profiles. Transcription profiles of CKS2, DTL, KIF2C, KPNA2, MYBL2, TPX2 and FBL provided clues of aberrantly methylation-based biomarkers, which might improve the development of precise medicine.

scholarly journals Gene expression and DNA methylation analyses suggest that two immune related genes are prognostic factors of colorectal cancer

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Xiao-Liang Xing ◽  
Zhi-Yong Yao ◽  
Chaoqun Xing ◽  
Zhi Huang ◽  
Jing Peng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Risk Assessment ◽  
Dna Methylation ◽  
Differentially Expressed Genes ◽  
Risk Score ◽  
Immune Cells ◽  
Assessment Model ◽  
Differentially Expressed ◽  
Risk Assessment Model

Abstract Background Colorectal cancer (CRC) is the second most prevalent cancer, as it accounts for approximately 10% of all annually diagnosed cancers. Studies have indicated that DNA methylation is involved in cancer genesis. The purpose of this study was to investigate the relationships among DNA methylation, gene expression and the tumor-immune microenvironment of CRC, and finally, to identify potential key genes related to immune cell infiltration in CRC. Methods In the present study, we used the ChAMP and DESeq2 packages, correlation analyses, and Cox regression analyses to identify immune-related differentially expressed genes (IR-DEGs) that were correlated with aberrant methylation and to construct a risk assessment model. Results Finally, we found that HSPA1A expression and CCRL2 expression were positively and negatively associated with the risk score of CRC, respectively. Patients in the high-risk group were more positively correlated with some types of tumor-infiltrating immune cells, whereas they were negatively correlated with other tumor-infiltrating immune cells. After the patients were regrouped according to the median risk score, we could more effectively distinguish them based on survival outcome, clinicopathological characteristics, specific tumor-immune infiltration status and highly expressed immune-related biomarkers. Conclusion This study suggested that the risk assessment model constructed by pairing immune-related differentially expressed genes correlated with aberrant DNA methylation could predict the outcome of CRC patients and might help to identify those patients who could benefit from antitumor immunotherapy.

The ERK pathway involves positive and negative regulations of HT-29 colorectal cancer cell growth by extracellular zinc

2003 ◽  
Vol 285 (6) ◽  
pp. G1181-G1188 ◽  
Author(s):  
Ki-Sook Park ◽  
Nam-Gu Lee ◽  
Ki-Hoo Lee ◽  
Jeong Taeg Seo ◽  
Kang-Yell Choi
Keyword(s):  
Colorectal Cancer ◽  
Signal Transduction ◽  
Cell Proliferation ◽  
Cell Growth ◽  
Cyclin D1 ◽  
Growth Regulation ◽  
Erk Pathway ◽  
Differential Growth ◽  
Erk Activation ◽  
Ht 29

Dietary zinc is an important trace element in the body and is related to both cell proliferation and growth arrest. A recent study found that extracellular zinc-sensing receptors trigger intracellular signal transduction in HT-29 human colorectal cancer cells. However, the signaling mechanism causing this growth regulation by extracellular zinc is not clearly understood. At 10- and 100-μM levels of ZnCl2 treatment, HT-29 cell growth and proliferation increased and decreased, respectively, in a minimally serum-starved medium (MSSM). A lack of significant increase in intracellular zinc levels after zinc treatment suggested that this differential growth regulation of HT-29 cells by extracellular zinc is acquired by receptor-mediated signal transduction. Moreover, this zinc-induced growth regulation was differentially affected by PD-98059, suggesting the involvement of the ERK pathway. Transient ERK activation and subsequent cyclin D1 induction were observed on adding 10 μM ZnCl2 in MSSM in the presence of cell proliferation. On the other hand, prolonged ERK activity was observed with a subsequent increase of cyclin D1 and p21Cip/WAF1 on adding 100 μM ZnCl2 in MSSM, and this was associated with nonproliferation. Moreover, this ERK activation and cyclin D1 and p21Cip/WAF1 induction were abolished by PD-98059 pretreatment. The differential regulations of cell growth, ERK activities, and cyclin D1 and p21Cip/WAF1 inductions were also observed in serum-enriched medium containing higher zinc concentrations. Therefore, differential cell cycle regulator induction occurs by a common ERK pathway in the differential growth regulation of HT-29 cells by extracellular zinc.

scholarly journals Effects of low-to-moderate ethanol consumption on colonic growth and gene expression in young adult and middle-aged male rats

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0243499
Author(s):  
Nicole Wells ◽  
Jacqueline Quigley ◽  
Jeremy Pascua ◽  
Natalie Pinkowski ◽  
Lama Almaiman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Cell Differentiation ◽  
Young Adult ◽  
Cell Growth ◽  
Alcohol Consumption ◽  
Ethanol Consumption ◽  
Ethanol Treatment ◽  
Middle Aged

Excessive alcohol consumption is a risk factor associated with colorectal cancer; however, some epidemiological studies have reported that moderate alcohol consumption may not contribute additional risk or may provide a protective effect reducing colorectal cancer risk. Prior research highlights the importance of proliferation, differentiation, and apoptosis as parameters to consider when evaluating colonic cell growth and tumorigenesis. The present study investigated whether chronic low-to-moderate ethanol consumption altered these parameters of colonic cell growth and expression of related genes. Twenty-four nondeprived young adult (109 days old) and 24 nondeprived middle-aged (420 days old) Wistar rats were randomly assigned to an ethanol-exposed or a water control group (n = 12/group). The ethanol group was provided voluntary access to a 20% v/v ethanol solution on alternate days for 13 weeks. Colon tissues were collected for quantitative immunohistochemical analyses of cell proliferation, differentiation and apoptosis using Ki-67, goblet cell and TUNEL, respectively. Gene expression of cyclin D1 (Ccnd1), Cdk2, Cdk4, p21waf1/cip1 (Cdkn1a), E-cadherin (Cdh1) and p53 were determined by quantitative real-time polymerase chain reaction in colonic scraped mucosa. Ethanol treatment resulted in a lower cell proliferation index and proliferative zone, and lower Cdk2 expression in both age groups, as well as trends toward lower Ccnd1 and higher Cdkn1a expression. Cell differentiation was modestly but significantly reduced by ethanol treatment only in older animals. Overall, older rats showed decreases in apoptosis and gene expression of Cdk4, Cdh1, and p53 compared to younger rats, but there was no observed effect of ethanol exposure on these measures. These findings suggest that low-to-moderate ethanol consumption improves at least one notable parameter in colonic tumorigenesis (cell proliferation) and associated gene expression regardless of age, however, selectively decreased cell differentiation among older subjects.

scholarly journals Genomic Expression Profiling of Colorectal Cancer in Silico

2021 ◽  
Author(s):  
Feifei Liu ◽  
Yu Wang ◽  
Wenxue Li ◽  
Diancheng Li ◽  
Yuwei Xin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Survival Analysis ◽  
Mrna Expression ◽  
Differentially Expressed Genes ◽  
Expression Profiles ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Analysis Tool ◽  
Hub Genes ◽  
Normal Tissues

Abstract Background: Colorectal cancer (CRC) is one of the most common malignancies of the digestive system; the progression and prognosis of which are affected by a complicated network of genes and pathways. The aim of this study was to identify potential hub genes associated with the progression and prognosis of colorectal cancer (CRC).Methods: We obtained gene expression profiles from GEO database to search differentially expressed genes (DEGs) between CRC tissues and normal tissue. Subsequently, we conducted a functional enrichment analysis, generated a protein–protein interaction (PPI) network to identify the hub genes, and analyzed the expression validation of the hub genes. Kaplan–Meier plotter survival analysis tool was performed to evaluate the prognostic value of hub genes expression in CRC patients.Results: A total of 370 samples, involving CRC and normal tissues were enrolled in this article. 283 differentially expressed genes (DEGs), including 62 upregulated genes and 221 downregulated genes between CRC and normal tissues were selected. We finally filtered out 6 hub genes, including INSL5, MTIM, GCG, SPP1, HSD11B2, and MAOB. In the database of TCGA-COAD, the mRNA expression of INSL5, MT1M, HSD11B2, MAOB in tumor is lower than that in normal; the mRNA expression of SPP1 in tumor is higher than that in normal. In the HPA database, the expression of INSL5, GCG, HSD11B2, MAOB in tumor is lower than that in normal tissues; the expression of SPP1 in the tumor is higher than that in normal tissues. Survival analysis revealed that INSL5, GCG, SPP1 and MT1M may serve as prognostic biomarkers in CRC. Conclusions: We screened out six hub genes to predict the occurrence and prognosis of patients with CRC using bioinformatics methods, which may provide new targets and ideas for diagnosis, prognosis and individualized treatment for CRC.

scholarly journals Dihydroartemisinin Inhibits Proliferation and Induces Apoptosis of Human Hepatocellular Carcinoma Cell by Upregulating Tumor Necrosis Factor via JNK/NF-κB Pathways

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Long Wu ◽  
Yanlei Cheng ◽  
Junjian Deng ◽  
Weiping Tao ◽  
Junjie Ye
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
Differentially Expressed Genes ◽  
Carcinoma Cell ◽  
Expression Profiles ◽  
Human Hepatocellular Carcinoma ◽  
Differentially Expressed ◽  
Venn Diagram ◽  
Dependent Manner ◽  
Hepatocellular Carcinoma Cell

Background. Dihydroartemisinin (DHA) is a predominant compound in Artemisia annua L., and it has been shown to inhibit tumorigenesis. Methods. In this study, the antitumor potential of DHA was investigated in the MHCC97-L hepatocellular carcinoma cell line. Cells were treated at various concentrations of DHA, and then the cell cycle, viability, and DNA synthesis were measured to evaluate cell proliferation. Furthermore, the expression of genes and proteins related to proliferation and apoptosis was measured to determine the effects of DHA. Finally, the mechanism was investigated using RNA-sequencing to identify differentially expressed genes and signaling pathways, and JNK/NF-κB pathways were evaluated with Western blotting. Results. Cells were treated with a concentration range of DHA from 1 to 100 μM, and cell proliferation was suppressed in a dose-dependent manner. In addition, the genes and proteins involved in typical cellular functions of MHCC97-L cells were significantly inhibited. DHA treatment downregulated the angiogenic gene ANGPTL2 and the cell proliferation genes CCND1, E2F1, PCNA, and BCL2. DHA treatment significantly upregulated the apoptotic genes CASP3, CASP8, CASP9, and TNF. Global gene expression profiles identified 2064 differentially expressed genes (DEGs). Among them, 744 were upregulated and 1320 were downregulated. Furthermore, MAPK, NF-kappa B, and TNF pathways were enriched based on the DEGs, and the consensus DEG was identified as TNF using a Venn diagram of those pathways. DHA promoted phosphorylation of JNK, inhibited nuclear p65, and then significantly induced TNF-α synthesis. Conclusion. DHA inhibited cell proliferation and induced apoptosis in human hepatocellular carcinoma cells by upregulating TNF expression via JNK/NF-κB pathways.

scholarly journals Interleukin-34 Enhances the Tumor Promoting Function of Colorectal Cancer-Associated Fibroblasts

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3537
Author(s):  
Eleonora Franzè ◽  
Antonio Di Grazia ◽  
Giuseppe Sigismondo Sica ◽  
Livia Biancone ◽  
Federica Laudisi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Cell Growth ◽  
Cancer Associated Fibroblasts ◽  
Cancer Cell Proliferation ◽  
Fibroblast Growth ◽  
Stromal Compartment ◽  
Large Numbers ◽  
And Migration ◽  
Proliferation And Migration

The stromal compartment of colorectal cancer (CRC) is marked by the presence of large numbers of fibroblasts, termed cancer-associated fibroblasts (CAFs), which promote CRC growth and progression through the synthesis of various molecules targeting the neoplastic cells. Interleukin (IL)-34, a cytokine over-produced by CRC cells, stimulates CRC cell growth. Since IL-34 also regulates the function of inflammatory fibroblasts, we hypothesized that it could regulate the tumor promoting function of colorectal CAFs. By immunostaining and real-time PCR, we initially showed that IL-34 was highly produced by CAFs and to lesser extent by normal fibroblasts isolated from non-tumoral colonic mucosa of CRC patients. CAFs and normal fibroblasts expressed the functional receptors of IL-34. IL-34 induced normal fibroblasts to express α-SMA, vimentin and fibroblast activation protein and enhanced fibroblast growth, thus generating a cellular phenotype resembling that of CAFs. Consistently, knockdown of IL-34 in CAFs with an antisense oligonucleotide (AS) decreased expression of such markers and inhibited cell proliferation. Co-culture of CRC cells with IL-34 AS-treated CAFs supernatants resulted in less cancer cell proliferation and migration. Among CAF-derived molecules known to promote CRC cell growth/migration, only netrin-1 and basic-fibroblast growth factor were induced by IL-34. Data suggest a role for IL-34 in the control of colorectal CAF function.

scholarly journals FOXE1 represses cell proliferation and Warburg effect by inhibiting HK2 in colorectal cancer

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Weixing Dai ◽  
Xianke Meng ◽  
Shaobo Mo ◽  
Wenqiang Xiang ◽  
Ye Xu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Poor Prognosis ◽  
Aerobic Glycolysis ◽  
Lactate Production ◽  
Glucose Consumption ◽  
Underlying Mechanism ◽  
Low Expression

Abstract Background Low expression of FOXE1, a member of Forkhead box (FOX) transcription factor family that plays vital roles in cancers, contributes to poor prognosis of colorectal cancer (CRC) patients. However, the underlying mechanism remains unclear. Materials and methods The effects of FOXE1 on the growth of colon cancer cells and the expression of glycolytic enzymes were investigated in vitro and in vivo. Molecular biological experiments were used to reveal the underlying mechanisms of altered aerobic glycolysis. CRC tissue specimens were used to determine the clinical association of ectopic metabolism caused by dysregulated FOXE1. Results FOXE1 is highly expressed in normal colon tissues compared with cancer tissues and low expression of FOXE1 is significantly associated with poor prognosis of CRC patients. Silencing FOXE1 in CRC cell lines dramatically enhanced cell proliferation and colony formation and promoted glucose consumption and lactate production, while enforced expression of FOXE1 manifested the opposite effects. Mechanistically, FOXE1 bound directly to the promoter region of HK2 and negatively regulated its transcription. Furthermore, the expression of FOXE1 in CRC tissues was negatively correlated with that of HK2. Conclusion FOXE1 functions as a critical tumor suppressor in regulating tumor growth and glycolysis via suppressing HK2 in CRC.

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