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

Graham, Lloyd D.; Pedersen, Susanne K.; Brown, Glenn; Ho, Thu; Kassir, Zena; Moynihan, Audrey T.; Vizgoft, Emma; Dunne, Robert; Pimlott, Letitia; Young, Graeme P.; LaPointe, Lawrence C.; Molloy, Peter L.

doi:10.1177/1947601911431081

Cited by 234 publications

(232 citation statements)

References 39 publications

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“…As the CRNDE promoter resides in the same CpG island as that of the adjacent IRX5 gene, methylation of the promoter region results in coordinated expression. 32 Similarly, we found that the highest positive correlation (0.77) for the lncRNA FENDRR was with a protein coding gene, FOXF1, transcribed bidirectionally on the opposite strand. 35 Additionally, the lncRNA HOTAIR, which resides in a HOXC gene cluster, is known to be co-expressed with HOXC genes, and overlaps HOXC11, displayed its highest positive correlation with multiple HOXC genes including HOXC11 (0.86), HOXC10 (0.72), HOXC13 (0.66), HOXC8 (0.44), and HOXC9 (0.38).…”

Section: Prediction Of Onco-lncrna Functionmentioning

confidence: 74%

Pan-cancer transcriptome analysis reveals long noncoding RNAs with conserved function

et al. 2015

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Section: Prediction Of Onco-lncrna Functionmentioning

confidence: 74%

Pan-cancer transcriptome analysis reveals long noncoding RNAs with conserved function

et al. 2015

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“…6,7,[79][80][81] Notably, similar to other nucleic acids, lncRNAs can also be present in peripheral blood components, such as serum, plasma, and peripheral blood mononuclear cells. [82][83][84] The peripheral lncRNA profiles may potentially contribute to the characterization of novel biomarkers for CRC patients. Indeed, some lncRNAs appear to have strong diagnostic potential as blood biomarkers for colorectal neoplasia.…”

Section: Tumor Diagnosismentioning

confidence: 99%

“…For example, the expression of colorectal neoplasia differentially expressed-h in the plasma had a sensitivity of 87% and a specificity of 93% for detecting CRC. 82 It is likely that circulating lncRNAs may represent new, relatively non-invasive molecular markers of tumor activity. However, no lncRNA-based diagnostics have been developed for use in CRC as of yet.…”

Section: Tumor Diagnosismentioning

confidence: 99%

Long non-coding RNAs in colorectal cancer: implications for pathogenesis and clinical application

Pan

2014

Modern Pathology

102

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Long non-coding RNAs (lncRNAs) are a class of newly identified non-coding RNA molecules that are emerging as key regulators of tumor initiation and development. Colorectal cancer (CRC) remains a major health problem worldwide, and there remains a need to further refine the current screening approaches as well as provide tailored diagnostic and therapeutic approaches. Multiple dysregulated lncRNAs participate in tumorigenesis through a variety of molecular mechanisms, and various regulatory factors frequently contribute to the aberrant expression of lncRNAs in CRC, thereby allowing malignant transformation. Additionally, the association of dysregulated lncRNAs with specific developmental stages and clinical outcomes indicates their potential as strong diagnostic and prognostic predictors as well as therapeutic targets. Here we provide a brief overview of the known functions of CRC-associated lncRNAs, describe some potential molecular mechanisms that underlie changes in lncRNA expression in CRC, and attempt to uncover their clinical and therapeutic potential. Keywords: colorectal cancer; diagnosis; dysregulation; long non-coding RNA; prognosis High-throughput genome-scale studies have demonstrated that more than 93% of the DNA sequences in the human genome are actively transcribed. 1 However, only approximately 5-10% of the sequences are stably transcribed into mRNA or non-coding RNA (ncRNA). Genome tiling arrays have revealed that the amount of non-coding sequence is at least four times larger than the amount of coding sequence, which indicates that only 1% of the human genome is composed of protein-coding genes and the remaining 4-9% is transcribed into ncRNAs. 2 Therefore, ncRNAs constitute a very large proportion of the total RNA molecules.The function and clinical significance of short regulatory ncRNAs, such as microRNAs (miRNAs) and small interfering RNAs (siRNAs), were elucidated first, 3 and the regulatory roles of miRNAs have been broadly recognized in almost all physiological and pathological processes in the body, including carcinogenesis. 4 For example, we previously reported that MIR95 promotes cell proliferation and targets sorting nexin 1 in human colorectal carcinoma; 5 moreover, in colorectal cancer (CRC) patients, the plasma levels of MIR29a and MIR92a are significantly upregulated and the plasma levels of MIR601 and MIR760 are significantly downregulated; thus the levels of these miRNAs have good diagnostic value for CRC screening. 6,7 According to their transcript size, ncRNAs are grouped into two major classes: (i) small ncRNAs with transcripts o200 nucleotides (nt; eg, aforementioned siRNAs and miRNAs, Piwi-interacting RNAs, and some retrotransposon-derived RNAs) and (ii) long non-coding RNAs (lncRNAs), this class includes five broad categories: sense, antisense, bidirectional, intronic, and intergenic, based on the proximity between neighboring transcripts. 8 For a time, lncRNAs was commonly defined as a proteincoding transcripts that is 4200 nt. 9 However, this definition is arbitrary and ...

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“…LncRNAs are involved in various physiological and cellular processes such as development, growth, cell cycle progression, differentiation, inflammation, tumorigenesis, migration and invasion [9-12, 21-23]. Colorectal neoplasia differentially expressed (CRNDE) was initially identified as an lncRNA in colorectal cancer and was found to be located on chromosome 16, which is important in the proliferation, migration, and invasion of colorectal tumor cells [24-28]. Nonetheless, little is known regarding the biological role of CNRDE in the process of colorectal cancer.…”

Section: Introductionmentioning

confidence: 99%

The Long Non-Coding RNA CRNDE Promotes Colorectal Carcinoma Progression by Competitively Binding miR-217 with TCF7L2 and Enhancing the Wnt/β-Catenin Signaling Pathway

et al. 2017

Cell Physiol Biochem

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Background/Aims: The long non-coding RNA colorectal neoplasia differentially expressed (CRNDE) contributes to the proliferation and migration of tumors. However, its molecular mechanism underlying gastric cancer remains unknown. In the present study, we investigated whether CRNDE was involved in the development of colorectal cancer via the binding of microRNA (miR)-217 with transcription factor 7-like 2 (TCF7L2) to enhance the Wnt signaling pathway. Methods: Quantitative polymerase chain reaction was used to detect CRNDE, miR-217 and TCF7L2 in colorectal cancer tissues and cells. The CCK-8 assay, wound healing assay, and Transwell assay were used to detect cell proliferation, migration and invasion, respectively. Western blotting and luciferase activity assays were used to identify CRNDE and TCF7L2 as one of the direct targets of miR-217. The activity of the Wnt/β-catenin signaling pathway was analyzed by the TOPflash assay, and the subcellular localization of β-catenin and TCF7L2 was analyzed by western blotting and confocal microscopy. Results: In this study, we found that high expression of CRNDE is negatively correlated with low expression of miR-217 in colorectal cancer tissue and colorectal cancer cells. The dual luciferase reporter analysis showed that miR-217 is bound to CRNDE and TCF7L2 and negatively regulate their expression. CRNDE down-regulation inhibited the cell proliferation, migration and invasion in vitro and in vivo and the inhibitions were both completely blocked after miR-217 inhibition or TCF7L2 overexpression. Finally, TOPflash analysis showed that the activity of Wnt/β-catenin signaling is inhibited by CRNDE down-regulation and rescued by TCF7L2 over-expression. Consistently immunostaining and western blotting analysis showed that the expression of b-catenin and TCF7L2 in the nucleus was significantly decreased by CRNDE down-regulation and was rescued by TCF7L2 over-expression. Conclusions: The present study suggest that CRNDE involves in the cell proliferation, migration and invasion of colorectal cancer cells via increasing the expression of TCF7L2 and activity of Wnt/β-catenin signaling through binding miR-217 competitively.

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

Cited by 234 publications

References 39 publications

Pan-cancer transcriptome analysis reveals long noncoding RNAs with conserved function

Pan-cancer transcriptome analysis reveals long noncoding RNAs with conserved function

Long non-coding RNAs in colorectal cancer: implications for pathogenesis and clinical application

The Long Non-Coding RNA CRNDE Promotes Colorectal Carcinoma Progression by Competitively Binding miR-217 with TCF7L2 and Enhancing the Wnt/β-Catenin Signaling Pathway

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