Phosphorylation of Cajal body protein coilin activated by UHMK1 influences the sensitivity of colon cancer cells to 5-FU
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PROVIDER: PRJNA714432 | ENA |
REPOSITORIES: ENA
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Project description:Drug resistance to 5-fluorouracil (5-FU) and recurrence after chemotherapy in colorectal cancer remain a challenge to be resolved for the improvement of patient outcomes. In the present study, we found that the application of conditioned medium (CM) derived from 5-FU-resistant colon cancer cells HCT-8/FU reduced the chemosensitivity of native HCT-8 to 5-FU, which was accompanied with the significant changes at number counts and morphology of Cajal bodys (CBs), a spherical nuclear body, dynamic exchanging constituent macromolecules (i.e., body-specific proteins and RNAs) with the nucleoplasmic space.It was shown that the disassembly and reassembly of CBs regulated by the phosphorylation of coilin, which was significantly activated by UHMK1. These led to a large number of variations of RNA alternative splicing in cells, which could contribute to the cell survival through remodeling of intracellular phenotype and transmitting preadaptive signal to adjacent cells in tumor microenvironment.
2021-03-15 | GSE168888 | GEO
Project description:5-Fluorouracil (5-FU) is one of the most common drugs used in chemotherapy because of its efficacy and stability. However, 5-FU has been known to work on only 10~15% of colon cancer patients. Therefore, the study of 5-FU sensitivity study is necessary to increase the survival of colon cancer patients. p53 is one of the factors that effect on drug sensitivity. Main function of p53 has been focused on transcription activity in cell death. Numerous drug related studies show that expression of wild-type p53 increases drug sensitivity in various cancer types through inducing apoptotic signaling pathways. Currently, it has been reported that p53 has both transcriptional and non-transcriptional activities in apoptosis. However, most studies about p53 non-transcriptional activities in apoptosis are mainly focused on p53 induced mitochondrial outer membrane permeabilization, triggering the release of pro-apoptotic factors. The chromatin structure and organization have strongly attracted because of their impacts in cellular phenotypes. Recent studies have been shown that changes in chromatin accessibility affect cell phenotypes for external stimuli. Since p53 plays an important role in drug sensitivity and 5-FU is an external stimulus for cancer cells, we hypothesized that p53 may effect on 5-FU sensitivity through different regulation of chromatin accessible regions between TP53-WT and TP53-KO cells. To determine the effect of p53 on chromatin accessibility modification associated with 5-FU sensitivity, ATAC-seq and RNA-seq were performed under 5-FU treatment on TP53-WT as drug sensitive and TP53-KO as drug resistant HCT116 cells. In this study, we found that 5-FU induces chromatin accessibility in both TP53-WT and TP53-KO cells. Moreover, our results show that 5-FU induced chromatin accessibility increases expression of apoptotic genes in TP53-WT HCT116 cells through p53 non-transcriptional activity in nucleus.
2021-02-10 | GSE157949 | GEO
Project description:5-Fluorouracil (5-FU) is one of the most common drugs used in chemotherapy because of its efficacy and stability. However, 5-FU has been known to work on only 10~15% of colon cancer patients. Therefore, the study of 5-FU sensitivity study is necessary to increase the survival of colon cancer patients. p53 is one of the factors that effect on drug sensitivity. Main function of p53 has been focused on transcription activity in cell death. Numerous drug related studies show that expression of wild-type p53 increases drug sensitivity in various cancer types through inducing apoptotic signaling pathways. Currently, it has been reported that p53 has both transcriptional and non-transcriptional activities in apoptosis. However, most studies about p53 non-transcriptional activities in apoptosis are mainly focused on p53 induced mitochondrial outer membrane permeabilization, triggering the release of pro-apoptotic factors. The chromatin structure and organization have strongly attracted because of their impacts in cellular phenotypes. Recent studies have been shown that changes in chromatin accessibility affect cell phenotypes for external stimuli. Since p53 plays an important role in drug sensitivity and 5-FU is an external stimulus for cancer cells, we hypothesized that p53 may effect on 5-FU sensitivity through different regulation of chromatin accessible regions between TP53-WT and TP53-KO cells. To determine the effect of p53 on chromatin accessibility modification associated with 5-FU sensitivity, ATAC-seq and RNA-seq were performed under 5-FU treatment on TP53-WT as drug sensitive and TP53-KO as drug resistant HCT116 cells. In this study, we found that 5-FU induces chromatin accessibility in both TP53-WT and TP53-KO cells. Moreover, our results show that 5-FU induced chromatin accessibility increases expression of apoptotic genes in TP53-WT HCT116 cells through p53 non-transcriptional activity in nucleus.
2021-02-10 | GSE157950 | GEO
Project description:To investigate location of Cajal bodies (CB) inside the cell nucleus, we created a stable cell line expressing the GFP version of CB-marker protein coilin at endogenous levels and performed ChIP-seq with anti-EGFP antibody. ChIP-seq revealed close association of CBs wih U3 genes, snRNA genes and histone genes in histone cluster 1 and 2. 1 biological replicate of coilin ChIP-seq and input sample
2014-11-06 | E-GEOD-58449 | biostudies-arrayexpress
Project description:p53 influences 5-FU-induced chromatin accessibility [ATAC-seq]
| PRJNA663471 | ENA
Project description:p53 influences 5-FU-induced chromatin accessibility [ChIP-seq]
| PRJNA663473 | ENA
Project description:TE-5 and 5-FU resistant subline TE-5R
2015-06-03 | GSE69494 | GEO
Project description:Coilin is a scaffold protein essential for the structural integrity of Cajal Bodies, which are non-membranous nuclear organelles that are thought to facilitate assembly and maturation of nuclear RNPs, including spliceosomal snRNPs. To investigate further coilin’s functions in plant cells, and to identify proteins that may functionally interact with coilin, we performed a genetic suppressor screen in Arabidopsis thaliana using a coilin (coi) mutant displaying altered splicing of a GFP pre-mRNA. The modified splicing pattern results in a ‘hyper-GFP’ phenotype in young coi seedlings relative to the intermediate level of GFP in wild-type seedlings. Additionally, in newly emerging leaves of older coi seedlings, the GFP gene frequently undergoes abrupt siRNA-associated posttranscriptional gene silencing that persists during growth. In the suppressor screen, we searched for mutations that subdue one or both of these GFP phenotypes and identified several understudied factors in plants: WRAP53, a putative Cajal body protein; SMU2, a predicted splicing-related factor; and ZC3HC1, an uncharacterized zinc finger protein. All three mutations return the hyper-GFP phenotype of the coi mutant to approximately the intermediate wild-type level. The zc3hc1 mutations in particular induce premature and more extensive posttranscriptional gene silencing similar to mutations in SOP1 and DCL4, which are known modifiers of posttranscriptional gene silencing. Candidate coilin-interacting proteins identified by immunoprecipitation-mass spectrometry include many splicing-related factors, nucleolar proteins, and mRNA export factors. Our results demonstrate the usefulness of the coi mutant to identify new modifiers of alternative splicing and posttranscriptional gene silencing, and suggest diverse roles for coilin in plant cells.
2023-07-27 | PXD027146 | Pride