Downregulation of three tumour suppressor genes SLC26A3, DCN and TPM1 in colorectal cancer
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE14010 | GEO | 2009/11/01
SECONDARY ACCESSION(S): PRJNA112473
REPOSITORIES: GEO
Similar Datasets
Project description:Despite identification of major genes and pathways involved in development of colorectal cancer (CRC) it became obvious that several steps in these pathways might be bypassed by other yet unknown genetic events that lead towards CRC. To improve our understanding of the genetic mechanisms of CRC development we used microarrays to identify novel genes involved in development of CRC. In order to identify possible novel genes involved in the development of colorectal cancer we analysed the expression profile of 16 colorectal cancers. We used dual color approach. Tumour tissue was labeled with Cy5 and corresponding normal tissue was labeled with Cy3. Each array contained at least 4 replicate spots for each gene analysed. Expression was obtained by calculating median from replicate spots. Genes not present in at least 100% of all samples were filtered out. Median value for each gene from 16 arrays was calculated.
2010-06-20 | E-GEOD-14010 | biostudies-arrayexpress
Project description:The radio-chemotherapy with 5-fluorouracil (5-FU) is the standard of care treatment for patients with locally advanced rectal cancer (LARC) but it is only effective for a third of them. The proteomic and transcriptomic response of three colorectal cancer (CRC) cell lines to 5-FU and radiation was assessed and correlated with their genetic background. The induction of a 5-FU-resistance in those cell lines negatively affects the levels of transcripts corresponding to Krüppel-associated box (KRAB)-containing zinc finger proteins (ZFPs), the largest family of transcriptional repressors. Among nearly 350 KRAB-ZFPs, almost a quarter are down-regulated after the induction of a 5-FU-resistance including a common one between the three CRC cell lines, ZNF649, whose role is still unknown. This proteomic, transcriptomic and genomic analysis of intrinsic and acquired resistance highlights possible new mechanisms involved in resistance to treatment and therefore potential new therapeutic targets to overcome this resistance.
2022-05-19 | PXD020000 | Pride
Project description:The radio-chemotherapy with 5-fluorouracil (5-FU) is the standard of care treatment for patients with locally advanced rectal cancer (LARC) but it is only effective for a third of them. The proteomic and transcriptomic response of three colorectal cancer (CRC) cell lines to 5-FU and radiation was assessed and correlated with their genetic background. The induction of a 5-FU-resistance in those cell lines negatively affects the levels of transcripts corresponding to Krüppel-associated box (KRAB)-containing zinc finger proteins (ZFPs), the largest family of transcriptional repressors. Among nearly 350 KRAB-ZFPs, almost a quarter are down-regulated after the induction of a 5-FU-resistance including a common one between the three CRC cell lines, ZNF649, whose role is still unknown. This proteomic, transcriptomic and genomic analysis of intrinsic and acquired resistance highlights possible new mechanisms involved in resistance to treatment and therefore potential new therapeutic targets to overcome this resistance.
2022-04-13 | GSE153412 | GEO
Project description:BackgroundDespite identification of the major genes and pathways involved in the development of colorectal cancer (CRC), it has become obvious that several steps in these pathways might be bypassed by other as yet unknown genetic events that lead towards CRC. Therefore we wanted to improve our understanding of the genetic mechanisms of CRC development.MethodsWe used microarrays to identify novel genes involved in the development of CRC. Real time PCR was used for mRNA expression as well as to search for chromosomal abnormalities within candidate genes. The correlation between the expression obtained by real time PCR and the presence of the KRAS mutation was investigated.ResultsWe detected significant previously undescribed underexpression in CRC for genes SLC26A3, TPM1 and DCN, with a suggested tumour suppressor role. We also describe the correlation between TPM1 and DCN expression and the presence of KRAS mutations in CRC. When searching for chromosomal abnormalities, we found deletion of the TPM1 gene in one case of CRC, but no deletions of DCN and SLC26A3 were found.ConclusionOur study provides further evidence of decreased mRNA expression of three important tumour suppressor genes in cases of CRC, thus implicating them in the development of this type of cancer. Moreover, we found underexpression of the TPM1 gene in a case of CRCs without KRAS mutations, showing that TPM1 might serve as an alternative path of development of CRC. This downregulation could in some cases be mediated by deletion of the TPM1 gene. On the other hand, the correlation of DCN underexpression with the presence of KRAS mutations suggests that DCN expression is affected by the presence of activating KRAS mutations, lowering the amount of the important tumour suppressor protein decorin.
| S-EPMC2745427 | biostudies-literature
Project description:RATIONALE: Genetic studies may help in understanding the genetic processes involved in the development of some types of cancer.
PURPOSE: Clinical trial to study the cancer-related genes in patients who have colon cancer or adenomatous polyps.
| 2008922 | ecrin-mdr-crc
Project description:Colorectal carcinoma is one of the most aggressive malignant epithelial neoplasms affecting the gastrointestinal tract. The incidence of colorectal carcinoma is obviously increasing in developing countries, where the physical inactivity and the consumption of animal fat-rich food became more evident. Colorectal tumorigenesis is a multistep process which is initiated by adenoma and is terminated by carcinoma, the latter shows variable degrees of tumor differentiation and invasiveness. During the adenoma-carcinoma process; a series of genetic mutations occur. Detection of these genetic mutations will help in the development of novel therapeutic agents, which in turn will improve patients’ outcomes. Cortactin (CTTN) is a Src kinase substrate, encoded by a gene located on chromosome 11. CTTN binds to and activates Arp 2/3 and stabilizes the dynamic actin assembly after its formation. So, it become clear that CTTN is involved in the formation of the leading-edges cellular protrusions.
| 2403606 | ecrin-mdr-crc
Project description:Colorectal cancer (CRC) is a genetically heterogeneous disease with several distinct morphological growth patterns. This study was aimed to investigate genes differentially expressed between ulcerative and polypoid colorectal CRC. cDNA microarray was first employed to compare the gene expression profiling of ulcerative and polypoid CRC with paired normal mucosa. Potential candidates identified by data filtering were further validated using quantitative real-time polymerase chain reaction, western blot and immunohistochemistry. Epigenetic regulation of gene expression was investigated using methylation-specific PCR (MSP). cDNA microarray identified 11 up-regulated and 14 down-regulated genes differentially expressed in both types of tumor compared to matched normal mucosa. Among them, S100P was the only upregulated gene preferentially associated with polypoid CRC (p = 0.032), whereas no genes demonstrated significantly differential association with ulcerative CRC. S100P protein and mRNA expression level of polypoid CRC was significantly higher than that of ulcerative CRC (p < 0.05, respectively). Immunoreactivity of S100P protein was localized predominantly in the nuclei and to a less extent in the cytoplasm. Overexpression of S100P occurred early in the adenoma stage. 80% (24/30) and 20% (6/30) polypoid CRC showed diffusely strong and moderate overexpression, respectively. In contrast, S100P was diffusely and strongly expressed in 15% (6/40) ulcerative CRC, with 52.5% (21/40) and 32.5% (13/40) tumors having moderate and weak overexpression, respectively. S100P overexpression was preferentially associated with polypoid CRC (p < 0.001). The relative methylation level determined by MSP was not statistically different between polypoid and ulcerative CRC (43.36% vs. 49.10%, p = 0.168), indicating that promoter hypomethylation was directly related to upregulation of S100P mRNA. The gene expression profiling of ulcerative and polypoid CRC with paired normal mucosa were compared. Dye swapping experiments with ulcerative CRC vs normal mucosa or polypoid CRC vs normal mucosa were performed and we averaged the log ratios of the duplicated spots on each slide.
2013-05-16 | E-GEOD-46905 | biostudies-arrayexpress
Project description:In this study, we conducted a microarray-based analysis to identify differentially expressed miRNAs in CRC by comparing miRNA profiles among primary CRC tissues from patients with liver metastases, primary tissues without liver metastases, and liver metastatic lesions. microRNAs (miRNAs) have been shown to have a potential for cancer diagnosis lately. The main objective of this study is to identify a novel biomarker serum miRNA from the patients with colorectal cancer (CRC). Microarray analysis of miRNA expression was performed using paired pre- and post- operative serum from 10 CRC patients. Two miRNAs (let-7a, miR-199a-3p) decreased significantly in the post-operative serum when compared to pre-operative serum (P=0.015 and 0.029, respectively). Microarrays were performed for the testing cohort of primary CRC lesions (n=28) and liver metastatic lesions (n=8).
2016-02-14 | E-GEOD-72199 | biostudies-arrayexpress
Project description:Cancer-related deregulation of miRNA biogenesis has been suggested, but the underlying mechanisms remain elusive. Here we report a previously unrecognized effect of hypoxia in the downregulation of Drosha and Dicer in cancer cells that leads to dysregulation of miRNA biogenesis and increased tumour progression. We show that hypoxia-mediated downregulation of Drosha is dependent on ETS1/ELK1 transcription factors. Moreover, mature miRNA array and deep sequencing studies reveal altered miRNA maturation in cells under hypoxic conditions. At a functional level, this phenomenon results in increased cancer progression in vitro and in vivo, and data from patient samples are suggestive of miRNA biogenesis downregulation in hypoxic tumours. Rescue of Drosha by siRNAs targeting ETS1/ELK1 in vivo results in significant tumour regression. These findings provide a new link in the mechanistic understanding of global miRNA downregulation in the tumour microenvironment.
| S-EPMC4215647 | biostudies-literature
Project description:Coiled-coil domain-containing 68 (CCDC68) plays different roles in cancer and is predicted as a tumor suppressor in human colorectal cancer (CRC). However, the specific role of CCDC68 in CRC and the underlying mechanisms remain unknown. Here, we showed that CCDC68 expression was lower in CRC than in corresponding normal tissues, and CCDC68 level was positively correlated with disease-free survival. Ectopic expression of CCDC68 decreased CRC cell proliferation in vitro and suppressed the growth of CRC xenograft tumors in vivo. CCDC68 caused G0/G1 cell cycle arrest, downregulated CDK4, and upregulated ITCH, the E3 ubiquitin ligase responsible for CDK4 protein degradation. This increased CDK4 degradation, which decreased CDK4 protein levels and inhibited CRC tumor growth. Collectively, the present results identify a novel CDK4 regulatory axis consisting of CCDC68 and ITCH, which suggest that CCDC68 is a promising target for the treatment of CRC.
2021-04-14 | PXD024343 | Pride