Dataset Information

Colorectal Neoplasia Differentially Expressed (CRNDE), a Novel Gene with Elevated Expression in Colorectal Adenomas and Adenocarcinomas.

ABSTRACT: An uncharacterized gene locus (Chr16:hCG_1815491), now named colorectal neoplasia differentially expressed (gene symbol CRNDE), is activated early in colorectal neoplasia. The locus is unrelated to any known protein-coding gene. Microarray analysis of 454 tissue specimens (discovery) and 68 previously untested specimens (validation) showed elevated expression of CRNDE in >90% of colorectal adenomas and adenocarcinomas. These findings were confirmed and extended by exon microarray studies and RT-PCR assays. CRNDE transcription start sites were identified in CaCo2 and HCT116 cells by 5'-RACE. The major transcript isoforms in colorectal cancer (CRC) cell lines and colorectal tissue are CRNDE-a, -b, -d, -e, -f, -h, and -j. Except for CRNDE-d, the known CRNDE splice variants are upregulated in neoplastic colorectal tissue; expression levels for CRNDE-h alone demonstrate a sensitivity of 95% and specificity of 96% for adenoma versus normal tissue. A quantitative RT-PCR assay measuring CRNDE-h RNA levels in plasma was (with a threshold of 2(-?Ct) = 2.8) positive for 13 of 15 CRC patients (87%) but only 1 of 15 healthy individuals (7%). We conclude that individual CRNDE transcripts show promise as tissue and plasma biomarkers, potentially exhibiting high sensitivity and specificity for colorectal adenomas and cancers.

SUBMITTER: Graham LD

PROVIDER: S-EPMC3278902 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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Colorectal Neoplasia Differentially Expressed (CRNDE), a Novel Gene with Elevated Expression in Colorectal Adenomas and Adenocarcinomas.

Graham Lloyd D LD Pedersen Susanne K SK Brown Glenn S GS Ho Thu T Kassir Zena Z Moynihan Audrey T AT Vizgoft Emma K EK Dunne Robert R Pimlott Letitia L Young Graeme P GP Lapointe Lawrence C LC Molloy Peter L PL

Genes & cancer 20110801 8

An uncharacterized gene locus (Chr16:hCG_1815491), now named colorectal neoplasia differentially expressed (gene symbol CRNDE), is activated early in colorectal neoplasia. The locus is unrelated to any known protein-coding gene. Microarray analysis of 454 tissue specimens (discovery) and 68 previously untested specimens (validation) showed elevated expression of CRNDE in >90% of colorectal adenomas and adenocarcinomas. These findings were confirmed and extended by exon microarray studies and RT- ...[more]

PMID: 22393467

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Project description:BackgroundThe incidence of anaplastic thyroid cancer (ATC) is high among human cancers. Colorectal neoplasia differentially expressed (CRNDE) is highly expressed in common tumors, and is therefore a potential molecular target for anti-tumor therapy. However, the function of CRNDE in ATC remains elusive.MethodsThe Gene Expression Omnibus (GEO) database was used to screen the differential expression of long-noncoding RNA (lncRNA) in ATC tissues. The Cancer Genome Atlas (TCGA) database was used to analyze the expression of CRNDE in thyroid cancer (THCA) tissues and its impact on patient prognosis. Quantitative real-time PCR (qRT-PCR) was used to determine the expression level of CRNDE in tumor and control tissues. The biological function of CRNDE in THCA was explored using TCGA RNA sequencing (RNA-seq) data analysis. ATC cell lines with low and high CRNDE expression were selected for CRNDE siRNA transfection, and the proliferation of cells was detected in each group.ResultsThe GEO and TCGA databases analysis results showed that CRNDE was highly expressed in ATC tissues, which is related to the poor prognosis of THCA patients. Also, the expression of CRNDE in the ATC cell line, ARO (human thyroid cancer cell line), was relatively high, while the expression in sw579 is relatively low. Therefore, ARO and sw579 were chosen for CRNDE small interfering RNA (siRNA) transfection. Compared with negative control (si-NC), the expression of CRNDE in si-CRNDE-1, si-CRNDE-2, and si-CRNDE-3 was reduced, indicating that the inhibitory effect was significantly enhanced and the cell proliferation ability was reduced, and the cell cycle is arrested in the G0/G1 phase. Finally, it was found that the wnt3a, β-catenin, and cyclinD1 protein expressions of si-CRNDE-1 and si-CRNDE-2 were significantly reduced.ConclusionsThe high expression of CRNDE in ATC tissues may promote the proliferation of ATC cells by regulating the Wnt/β-catenin signaling pathway. CRNDE may be a potential molecular target for the treatment of ATC.

Project description:BackgroundInflammation is believed to influence human colorectal carcinogenesis and may have an impact on prognosis and survival. The mucosal immunophenotype in dogs with colorectal cancer is poorly described. The aim of this study was to investigate whether the density, distribution and grade of tumor-infiltrating immune cells (TIIs) are different in normal colonic tissue vs benign stages (adenomas) and malignant stages (adenocarcinomas) of canine colorectal carcinogenesis, and thus, whether they can be considered as prognostic factors in dogs. This retrospective case-control study was performed on formalin-fixed, paraffin-embedded tissue samples from dogs with histologically confirmed colorectal adenoma (n = 18) and adenocarcinoma (n = 13) collected from archived samples. The samples had been collected by colonoscopy, surgery or during postmortem examination. Healthy colonic tissue obtained post mortem from dogs euthanized for reasons not involving the gastrointestinal tract served as control tissue (n = 9).ResultsThe tumor samples had significantly lower numbers of CD3+ T-cells in the epithelium compared to controls (adenocarcinoma vs control, Kruskal-Wallis test, p = 0.0004, and adenoma vs control, p = 0.002). Adenomas had a significantly lower number of CD18+ cells in the lamina propria, compared to control samples (Kruskal-Wallis test, p = 0.008). Colonic samples from control dogs had uniform staining of β-catenin along the cell membrane of epithelial cells. Compared to normal colonic cells, the expression levels of cytoplasmic β-catenin were significantly higher in adenomas and adenocarcinomas (adenoma vs control Kruskal-Wallis test, p = 0.004, and adenocarcinoma vs control, p = 0.002). None of the control samples showed positive staining of β-catenin in the nucleus of colonic cells. In contrast, adenocarcinomas and adenomas showed moderate to strong staining of the cell nucleus. The nuclear β-catenin expression (signal strength and distribution) was significantly higher in adenomas compared to adenocarcinomas (Kruskal-Wallis test, p < 0.05).Conclusionsβ-catenin and Ki67 were not useful markers for demonstrating tumor progression from adenomas to adenocarcinomas. The lower presence of CD18 and CD3+ cells in colorectal tumors compared to controls indicates a reduced presence of histiocytes and T-cells, which may have implications for the pathogenesis and progression of colorectal cancer in dogs.

Project description:Long noncoding RNAs (lncRNAs) play critical roles in the tumorigenesis and progression of hepatocellular carcinoma (HCC). As the most common malignant cancer type in humans, HCC poses a great threat to human health. However, the function of lncRNA colorectal neoplasia differentially expressed (CRNDE) in HCC has not been extensively studied. The chief aim of the present study was to reveal the potential role of CRNDE in HCC. Expression levels of CRNDE in HCC tissues and cell lines were detected by reverse transcription‑quantitative (RT‑q) PCR, and Cell Counting kit 8, wound‑healing and Transwell assays were used to evaluate the influences of CRNDE on in vitro cellular proliferation, migration and invasiveness, respectively. The interaction between CRNDE and microRNA (miR)‑29c‑3p was determined by dual‑luciferase reporter assay, and rescue experiments were conducted to evaluate the interactive relationships between CRNDE and miR‑29c‑3p or nuclear autoantigenic sperm protein (NASP). CRNDE was found to be upregulated in HCC tissues and cells, and to be positively associated with the poor prognosis of patients with HCC. Furthermore, CRNDE‑knockdown suppressed cell proliferation, migration and invasion abilities. Bioinformatics and RT‑qPCR analysis indicated miR‑29c‑3p as a potential target of CRNDE. In line with previous reports, as a tumor suppressor, downregulated expression of miR‑29c‑3p was observed in HCC. In addition, the present study revealed that miR‑29c‑3p directly targeted NASP. NASP expression was markedly elevated following transfection with an miR‑29c‑3p inhibitor, while knocking down CRNDE inhibited NASP expression. Moreover, the effects of CRNDE and NASP on HCC cells were reversed by miR‑29c‑3p. Collectively, the results of the present study revealed that CRNDE was upregulated and exerted an oncogenic role in HCC by targeting miR‑29c‑3p, and that the upregulation of CRNDE also promoted NASP expression. These findings indicate a novel role for CRNDE in the progression of HCC.

Project description:BackgroundThe methylation of the CpG islands of the LINE-1 promoter is a tight control mechanism on the function of mobile elements. However, simultaneous quantification of promoter methylation and transcription of LINE-1 has not been performed in progressive stages of colorectal cancer. In addition, the insertion of mobile elements in the genome of advanced adenoma stage, a precancerous stage before colorectal carcinoma has not been emphasized. In this study, we quantify promoter methylation and transcripts of LINE-1 in three stages of colorectal non-advanced adenoma, advanced adenoma, and adenocarcinoma. In addition, we analyze the insertion of LINE-1, Alu, and SVA elements in the genome of patient tumors with colorectal advanced adenomas.MethodsLINE-1 hypomethylation status was evaluated by absolute quantitative analysis of methylated alleles (AQAMA) assay. To quantify the level of transcripts for LINE-1, quantitative RT-PCR was performed. To find mobile element insertions, the advanced adenoma tissue samples were subjected to whole genome sequencing and MELT analysis.ResultsWe found that the LINE-1 promoter methylation in advanced adenoma and adenocarcinoma was significantly lower than that in non-advanced adenomas. Accordingly, the copy number of LINE-1 transcripts in advanced adenoma was significantly higher than that in non-advanced adenomas, and in adenocarcinomas was significantly higher than that in the advanced adenomas. Whole-genome sequencing analysis of colorectal advanced adenomas revealed that at this stage polymorphic insertions of LINE-1, Alu, and SVA comprise approximately 16%, 51%, and 74% of total insertions, respectively.ConclusionsOur correlative analysis showing a decreased methylation of LINE-1 promoter accompanied by the higher level of LINE-1 transcription, and polymorphic genomic insertions in advanced adenoma, suggests that the early and advanced polyp stages may host very important pathogenic processes concluding to cancer.

Dataset Information

Colorectal Neoplasia Differentially Expressed (CRNDE), a Novel Gene with Elevated Expression in Colorectal Adenomas and Adenocarcinomas.

Publications

Colorectal Neoplasia Differentially Expressed (CRNDE), a Novel Gene with Elevated Expression in Colorectal Adenomas and Adenocarcinomas.

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