Association between genetic variants in the promoter region of a novel antisense long noncoding RNA <i>RP11‐392P7.6</i> and colorectal cancer risk

Jin, Mingjuan; Gu, Simeng; Ding, Ye; Li, Yingjun; Jing, Fangyuan; Li, Qilong; Chen, Kun

doi:10.1002/em.22100

Cited by 8 publications

(5 citation statements)

References 49 publications

(56 reference statements)

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“…Participants with colorectal polyps (hyperplastic polyp or adenoma) were drawn from a population-based cohort since 1989 in Jiashan County, Zhejiang Province, China. It has been described in detail previously [22, 23]. For each participant, a histologically confirmed colorectal lesion (hyperplastic polyp, adenoma, or carcinoma) and a distant normal mucosa sample were obtained.…”

Section: Methodsmentioning

confidence: 99%

Genome-wide methylation profiling identified novel differentially hypermethylated biomarker MPPED2 in colorectal cancer

Lin

Ding

et al. 2019

Clin Epigenet

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Background Epigenetic alternation is a common contributing factor to neoplastic transformation. Although previous studies have reported a cluster of aberrant promoter methylation changes associated with silencing of tumor suppressor genes, little is known concerning their sequential DNA methylation changes during the carcinogenetic process. The aim of the present study was to address a genome-wide search for identifying potentially important methylated changes and investigate the onset and pattern of methylation changes during the progression of colorectal neoplasia. Methods A three-phase design was employed in this study. In the screening phase, DNA methylation profile of 12 pairs of colorectal cancer (CRC) and adjacent normal tissues was analyzed by using the Illumina MethylationEPIC BeadChip. Significant CpG sites were selected based on a cross-validation analysis from The Cancer Genome Atlas (TCGA) database. Methylation levels of candidate CpGs were assessed using pyrosequencing in the training dataset (tumor lesions and adjacent normal tissues from 46 CRCs) and the validation dataset (tumor lesions and paired normal tissues from 13 hyperplastic polyps, 129 adenomas, and 256 CRCs). A linear mixed-effects model was used to examine the incremental changes of DNA methylation during the progression of colorectal neoplasia. Results The comparisons between normal and tumor samples in the screening phase revealed an extensive CRC-specific methylomic pattern with 174,006 (21%) methylated CpG sites, of which 22,232 (13%) were hyermethylated and 151,774 (87%) were hypomethylated. Hypermethylation mostly occurred in CpG islands with an overlap of gene promoters, while hypomethylation tended to be mapped far away from functional regions. Further cross validation analysis from TCGA dataset confirmed 265 hypermethylated promoters coupling with downregulated gene expression. Among which, hypermethylated changes in MEEPD2 promoter was successfully replicated in both training and validation phase. Significant hypermethylation appeared since precursor lesions with an extensive modification in CRCs. The linear mixed-effects modeling analysis found that a cumulative pattern of MPPED2 methylation changes from normal mucosa to hyperplastic polyp to adenoma, and to carcinoma ( P < 0.001). Conclusions Our findings indicate that epigenetic alterations of MPPED2 promoter region appear sequentially during the colorectal neoplastic progression. It might be able to serve as a promising biomarker for early diagnosis and stage surveillance of colorectal tumorigenesis. Electronic supplementary material The online version of this article (10.1186/s13148-019-0628-y) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

Genome-wide methylation profiling identified novel differentially hypermethylated biomarker MPPED2 in colorectal cancer

Lin

Ding

et al. 2019

Clin Epigenet

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“…The third study focused on the promoter region of lncRNA RP11-392P7.6 which is an antisense to the G-protein coupled receptor family C group 5-member D (CPRC5D) a coding region of the cancer-related gene. The SNP rs10845671 on lncRNA RP11-392P7.6 is associated with an increased risk of CRC, indicating that it may contribute to the CRC susceptibility and may be a candidate biomarker for CRC risk prediction [49]. LncRNA colorectal cancer associated transcript 1 (CCAT1) is a relatively novel lncRNA, whose over-expression is demonstrated in early stage of tumorigenesis and in later disease phases of CRC.…”

Section: Methods For Detection Of Snps and Measurement Of Associatmentioning

confidence: 99%

SNPs and Somatic Mutation on Long Non-Coding RNA: New Frontier in the Cancer Studies?

et al. 2018

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In the last decade, it has been demonstrated that long non-coding RNAs (lncRNAs) are involved in cancer development. The great majority of studies on lncRNAs report alterations, principally on their expression profiles, in several tumor types with respect to the normal tissues of origin. Conversely, since lncRNAs constitute a relatively novel class of RNAs compared to protein-coding transcripts (mRNAs), the landscape of their mutations and variations has not yet been extensively studied. However, in recent years an ever-increasing number of articles have described mutations of lncRNAs. Single-nucleotide polymorphisms (SNPs) that occur within the lncRNA transcripts can affect the structure and function of these RNA molecules, while the presence of a SNP in the promoter region of a lncRNA could alter its expression level. Also, somatic mutations that occur within lncRNAs have been shown to exert important effects in cancer and preliminary data are promising. Overall, the evidence suggests that SNPs and somatic mutation on lncRNAs may play a role in the pathogenesis of cancer, and indicates strong potential for further development of lncRNAs as biomarkers.

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“…lncRNA RP11‐362K14.5 SNP rs1317082 T > C reduced the expression of CCSlnc362 by creating a bind site for miR‐4658, thus decreased the risk of CRC 38 . A novel SNP rs10845671, locating in lncRNA RP11‐392P7.6 promoter region, was associated with the susceptibility of CRC 39 . Our previous study has shown that MALAT1 rs664589 G allele upregulated MALAT1 expression by binding miR‐194‐5p and promoted CRC development 40 .…”

Section: Discussionmentioning

confidence: 94%

MAGI2‐AS3 rs7783388 polymorphism contributes to colorectal cancer risk through altering the binding affinity of the transcription factor GR to the MAGI2‐AS3 promoter

Yang

et al. 2020

Clinical Laboratory Analysis

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Background It has been indicated that the single nuclear polymorphisms (SNPs) in the long noncoding RNA (lncRNA) have association with colorectal cancer (CRC) susceptibility. Methods We enrolled 1078 cases with CRC and 1175 age‐ and gender‐matched cancer‐free controls to explore whether the polymorphisms in MAGI2‐AS3 have associations with CRC risk. qRT‐PCR, expression quantitative trait loci (eQTL) analyses, dual‐luciferase reporter assay, chromatin immunoprecipitation (ChIP), flow cytometry, and transwell assays were performed to explore the specific mechanisms in which MAGI2‐AS3 rs7783388 variation influenced the tumorigenesis of CRC. Results Subjects carrying rs7783388 GG genotype presented a higher risk of CRC compared with the AG/AA genotypes. Mechanistically, we found that the functional genetic variant of rs7783388 A > G decreased binding affinity of transcription factor glucocorticoid receptor (GR) to the MAGI2‐AS3 promoter, resulting in decreased transcriptional activity that subsequently downregulated MAGI2‐AS3 expression. Furthermore, functional experiments elucidated that MAGI2‐AS3 overexpression suppressed CRC cell proliferation, migration, and invasion capacities, arrested cell cycle at G0/G1 phase, and promoted cell apoptosis. Conclusion Taken together, our study demonstrated that the potential function of MAGI2‐AS3 as a tumor suppressor for CRC, and the MAGI2‐AS3 rs7783388 polymorphism is associated with the increased susceptibility to CRC by altering the binding ability of GR to the MAGI2‐AS3 promoter.

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Association between genetic variants in the promoter region of a novel antisense long noncoding RNA RP11‐392P7.6 and colorectal cancer risk

Cited by 8 publications

References 49 publications

Genome-wide methylation profiling identified novel differentially hypermethylated biomarker MPPED2 in colorectal cancer

Genome-wide methylation profiling identified novel differentially hypermethylated biomarker MPPED2 in colorectal cancer

SNPs and Somatic Mutation on Long Non-Coding RNA: New Frontier in the Cancer Studies?

MAGI2‐AS3 rs7783388 polymorphism contributes to colorectal cancer risk through altering the binding affinity of the transcription factor GR to the MAGI2‐AS3 promoter

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