Dataset Information

Hypermethylation of tumor suppressor lncRNA MEF2C-AS1 frequently happened in patients at all stages of colorectal carcinogenesis.

ABSTRACT:

Background

The novel long noncoding RNA MEF2C-AS1 has been identified to play suppressor roles during tumorigenesis. DNA methylation has a regulatory effect on gene expression in cancer initiation and progression. However, the methylation status of MEF2C-AS1 and its role in colorectal cancer (CRC) development remain unclear.

Methods

The expression and methylation levels of MEF2C-AS1 were systematically analyzed among 31 cancers with available qualified data in GEPIA and UCSC Xena databases. Then, the MEF2C-AS1 methylation status was firstly examined among 12 CRCs by Illumina Infinium MethylationEPIC BeadChip in in-house step 1 and further quantified among 48 CRCs by the MassARRAY method in in-house step 2. Subsequently, its methylation and expression levels were quantified among 81 non-advanced adenomas (NAAs), 81 advanced adenomas (AAs), and 286 CRCs using the MassARRAY method, and among 34 NAAs, 45 AAs, and 75 CRCs by qRT-PCR, in in-house step 3, respectively. The effect of MEF2C-AS1 methylation on CRC survival was analyzed by the Kaplan-Meier method. Additionally, in vitro cell proliferation, migration and invasion assays, and bioinformatics analysis were performed to explore the role of MEF2C-AS1 in colorectal carcinogenesis.

Results

Lower expression and higher methylation of MEF2C-AS1 were found in CRC by online databases. In the comparisons of lesion tissues with adjacent normal tissues, MEF2C-AS1 hypermethylation of each individual site and mean level was found among CRC patients in in-house step 1 and step 2, more meaningfully, among NAA patients, AA patients, and CRC patients at all stages during colorectal carcinogenesis in in-house step 3 (all p < 0.05). Further comparisons demonstrated significant differences between CRC and NAA (p = 0.025), AA and NAA (p = 0.020). Moreover, MEF2C-AS1 hypermethylation was associated with poorer disease-specific survival of CRC patients (p = 0.044). In addition, hypermethylation and lower expression of MEF2C-AS1 were verified in RKO cells, and the MEF2C-AS1 overexpression significantly suppressed RKO cell proliferation, migration, and invasion.

Conclusions

The findings reveal that MEF2C-AS1 hypermethylation might be an early driven event during colorectal carcinogenesis. It might serve as a promising prognostic biomarker for CRC survival. Our study also indicates the potential tumor-suppressing role of MEF2C-AS1 in CRC.

SUBMITTER: Qian S

PROVIDER: S-EPMC9446566 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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Publications

Hypermethylation of tumor suppressor lncRNA MEF2C-AS1 frequently happened in patients at all stages of colorectal carcinogenesis.

Qian Sangni S Lin Shujuan S Xu Xin X Bai Hao H Yeerken Aibuta A Ying Xiaojiang X Li Zhenjun Z Fei Xinglin X Yang Jinhua J Tang Mengling M Wang Jianbing J Jin Mingjuan M Chen Kun K

Clinical epigenetics 20220905 1

<h4>Background</h4>The novel long noncoding RNA MEF2C-AS1 has been identified to play suppressor roles during tumorigenesis. DNA methylation has a regulatory effect on gene expression in cancer initiation and progression. However, the methylation status of MEF2C-AS1 and its role in colorectal cancer (CRC) development remain unclear.<h4>Methods</h4>The expression and methylation levels of MEF2C-AS1 were systematically analyzed among 31 cancers with available qualified data in GEPIA and UCSC Xena ...[more]

PMID: 36064442

Similar Datasets

Project description:Background: Knowledge about the prognostic role of long noncoding RNA (lncRNA) in colorectal cancer (CRC) is limited. Therefore, we constructed a lncRNA-related prognostic model based on data from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). Materials and Methods: CRC transcriptome and clinical data were downloaded from the GSE20916 dataset and the TCGA database, respectively. R software was used for data processing and analysis. The differential lncRNA expression within the two datasets was first screened, and then intersections were measured. Cox regression and the Kaplan-Meier method were used to evaluate the effects of various factors on prognosis. The area under the curve (AUC) of the receiver operating characteristic curve and a nomogram based on multivariate Cox analysis were used to estimate the prognostic value of the lncRNA-related model. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were applied to elucidate the significantly involved biological functions and pathways. Results: A total of 11 lncRNAs were crossed. The univariate Cox analysis screened out two lncRNAs, which were analyzed in the multivariate Cox analysis. A nomogram based on the two lncRNAs and other clinicopathological risk factors was constructed. The AUC of the nomogram was 0.56 at 3 years and 0.71 at 5 years. The 3-year nomogram model was compared with the ideal model, which showed that some indices of the 3-year model were consistent with the ideal model, suggesting that our model was highly accurate. The GO and KEGG enrichment analyses showed that positive regulation of secretion by cells, positive regulation of secretion, positive regulation of exocytosis, endocytosis, and the calcium signaling pathway were differentially enriched in the two-lncRNA-associated phenotype. Conclusions: A two-lncRNA prognostic model of CRC was constructed by bioinformatics analysis. The model had moderate prediction accuracy. LncRNA BBOX1-AS1 and lncRNA FOXP4-AS1 were identified as prognostic biomarkers.

Dataset Information

Hypermethylation of tumor suppressor lncRNA MEF2C-AS1 frequently happened in patients at all stages of colorectal carcinogenesis.

Background

Methods

Results

Conclusions

Publications

Hypermethylation of tumor suppressor lncRNA MEF2C-AS1 frequently happened in patients at all stages of colorectal carcinogenesis.

Similar Datasets

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