N-Glycomic and Transcriptomic Changes Associated with CDX1 mRNA Expression in Colorectal Cancer Cell Lines

The caudal-related homeobox protein 1 (CDX1) is a transcription factor, which is important in the development, differentiation, and homeostasis of the gut. Although the involvement of CDX genes in the regulation of the expression levels of a few glycosyltransferases has been shown, associations between glycosylation phenotypes and CDX1 mRNA expression have hitherto not been well studied. Triggered by our previous study, we here characterized the N-glycomic phenotype of 16 colon cancer cell lines, selected for their differential CDX1 mRNA expression levels. We found that high CDX1 mRNA expression associated with a higher degree of multi-fucosylation on N-glycans, which is in line with our previous results and was supported by up-regulated gene expression of fucosyltransferases involved in antenna fucosylation. Interestingly, hepatocyte nuclear factors (HNF)4A and HNF1A were, among others, positively associated with high CDX1 mRNA expression and have been previously proven to regulate antenna fucosylation. Besides fucosylation, we found that high CDX1 mRNA expression in cancer cell lines also associated with low levels of sialylation and galactosylation and high levels of bisection on N-glycans. Altogether, our data highlight a possible role of CDX1 in altering the N-glycosylation of colorectal cancer cells, which is a hallmark of tumor development.

Download Full-text

MicroRNA silencing of CNN1 and CNN2 protein family members regulates biology processes in colorectal cancer by targeting the p53 signal pathway

10.21203/rs.3.rs-38064/v1 ◽

2020 ◽

Author(s):

Fuda Huang ◽

Mingwei Wei ◽

Anmin Wang ◽

Ya Zhang ◽

Zebang Qin ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Cycle ◽

Colon Cancer ◽

Cell Lines ◽

Cancer Cell ◽

Cancer Cell Lines ◽

Colon Cancer Cell ◽

Expression Levels ◽

Colon Cancer Cell Lines ◽

Cancer Tissues

Abstract BackgroundCalponin was first defined as a striated muscle troponin T-like protein that binds actin thin filaments to regulate smooth muscle contraction. There are few studies of CNN1 and CNN2 in colorectal cancer, and the roles these two genes play in colorectal cancer cell lines and the mechanisms by which they act are unknown.MethodsWe used immunohistochemistry to identify expression of the two genes in the cancer tissues. RT-PCR was used to measure expression levels of microRNA. W performed western blots to measure changes in signaling pathways in the context of expression interference.Meanwhile, the same method was used to measure binding relationship between the two genes and key pathway proteins. To determine the relationship between microRNA and gene mRNA, we used the reporter gene method. We used the chi-square and t-test methods to analyze the significance and correlations of the data.Results and conclusionsExpression levels of CNN1 were lower in colon cancer tissues than in normal mucosal tissues. After downregulating CNN1, the cell cycle in colon cancer cell lines progressed quickly, and the expression of related pathway proteins also increased. Expression levels of CNN2 were higher in colon cancer tissues, and its downregulation significantly inhibited cell cycle progression in colon cancer cell lines. We confirmed correlations between the expression of microRNA and CNN2 using data analysis.Bars indicate ± standard errors.*p < 0.05; **p < 0.01 compared with the control. The inhibition of the expression of CNN2 mRNA using microRNA was confirmed using western blot. The combination of the two at the mechanism level was also demonstrated using the reporter gene method.

Download Full-text

Development of a Gene Expression Panel, for the Prediction of Protein Abundances in Cancer Cell Lines

Current Bioinformatics ◽

10.2174/1574893616666210517162530 ◽

2021 ◽

Vol 16 ◽

Author(s):

Gunhee Lee ◽

Yeun-Jun Chung ◽

Minho Lee

Keyword(s):

Gene Expression ◽

Mrna Expression ◽

Cell Lines ◽

Cancer Cell ◽

Prediction Models ◽

Cancer Cell Lines ◽

Support Vector ◽

Rna Expression ◽

Expression Levels ◽

Protein Levels

Background: Due to the ease of quantifying mRNA expression in comparison with that of protein abundances, many studies have utilized it to infer protein product quantification. However, the mRNA expression values for a gene and its protein products are not known to have a strong relationship, because of the complex mechanisms required to regulate the amounts of protein levels, from translation to post-translational modifications. Methods: We have developed, in this study, models to predict protein levels from mRNA expression levels using the transcriptome and reverse phase protein arrays (RPPA)-based on protein levels in pan-cancer cell lines. When predicting the abundance of a protein expression, in addition to using RNA expression of the corresponding gene, we also used RNA expression levels of a particular set of other genes. By applying support vector regression, we have identified a 47-gene expression panel that contributes to the improved performance of the prediction, and its optimal subsets specific to each protein species. Result and Conclusion: Eventually, our final prediction models doubled the number of predictable protein expressions (r > 0.7). Due to the weaknesses of RPPA, our model had some limitations, however, we expect that these prediction models and the panel can be widely used in the future to infer protein abundances.

Download Full-text

Correlations of partial and extensive methylation at the p14ARF locus with reduced mRNA expression in colorectal cancer cell lines and clinicopathological features in primary tumors

Carcinogenesis ◽

10.1093/carcin/21.11.2057 ◽

2000 ◽

Vol 21 (11) ◽

pp. 2057-2064 ◽

Cited By ~ 61

Author(s):

S. Zheng

Keyword(s):

Colorectal Cancer ◽

Mrna Expression ◽

Cell Lines ◽

Cancer Cell ◽

Cancer Cell Lines ◽

Clinicopathological Features ◽

Colorectal Cancer Cell ◽

Primary Tumors ◽

Colorectal Cancer Cell Lines

Download Full-text

N-glycosylation Profiling of Colorectal Cancer Cell Lines Reveals Association of Fucosylation with Differentiation and Caudal Type Homebox 1 (CDX1)/Villin mRNA Expression

Molecular & Cellular Proteomics ◽

10.1074/mcp.m115.051235 ◽

2015 ◽

Vol 15 (1) ◽

pp. 124-140 ◽

Cited By ~ 40

Author(s):

Stephanie Holst ◽

Anna J. M. Deuss ◽

Gabi W. van Pelt ◽

Sandra J. van Vliet ◽

Juan J. Garcia-Vallejo ◽

...

Keyword(s):

Colorectal Cancer ◽

Mrna Expression ◽

Cell Lines ◽

Cancer Cell ◽

Cancer Cell Lines ◽

Colorectal Cancer Cell ◽

Colorectal Cancer Cell Lines

Download Full-text

Differential Expression of the Sphingolipid Pathway Is Associated with Sensitivity to the PP2A Activator FTY720 in Colorectal Cancer Cell Lines

Journal of Clinical Medicine ◽

10.3390/jcm10214999 ◽

2021 ◽

Vol 10 (21) ◽

pp. 4999

Author(s):

Peter Sciberras ◽

Laura Grech ◽

Godfrey Grech

Keyword(s):

Colorectal Cancer ◽

Mrna Expression ◽

Differential Expression ◽

Cell Lines ◽

Cancer Cell ◽

Aurora Kinase ◽

Cancer Cell Lines ◽

Breast Cancer Cell Lines ◽

Induced Apoptosis ◽

Ht 29

Protein phosphatase 2A (PP2A) is a ubiquitously expressed intracellular serine/threonine phosphatase. Deregulation of PP2A is a common event associated with adenocarcinomas of the colon and rectum. We have previously shown that breast cancer cell lines are sensitive to the PP2A activator FTY720, and that sensitivity is predicted by high Aurora kinase A (AURKA) mRNA expression. In this study, we hypothesized that high relative AURKA expression could predict sensitivity to FTY720-induced apoptosis in colorectal cancer (CRC). The CRC cell lines NCI H716, COLO320DM, DLD-1, SW480, and HT-29 show a high relative AURKA expression as compared to LS411N, T84, HCT116, SW48, and LOVO. Following viability assays, LS411N, T84, HCT116, and SW480 were shown to be sensitive to FTY720, whereas DLD-1 and HT-29 were non-sensitive. Hence, AURKA mRNA expression does not predict sensitivity to FTY720 in CRC cell lines. Differentially expressed genes (DEGs) were obtained by comparing the sensitive CRC cell lines (LS411N and HCT116) against the non-sensitive (HT-29 and DLD-1). We found that 253 genes were significantly altered in expression, and upregulation of CERS4, PPP2R2C, GNAZ, PRKCG, BCL2, MAPK12, and MAPK11 suggests the involvement of the sphingolipid signaling pathway, known to be activated by phosphorylated-FTY720. In conclusion, although AURKA expression did not predict sensitivity to FTY720, it is evident that specific CRC cell lines are sensitive to 5 µM FTY720, potentially because of the differential expression of genes involved in the sphingolipid pathway.

Download Full-text