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| Status |
Public on Dec 26, 2015 |
| Title |
Association between Hypomethylation of Noncoding Regions and Overexpression of the lnc-RNA, AFAP1-AS1, in Barrett’s Esophagus |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by high throughput sequencing
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| Summary |
Background & Aims: Alterations in methylation of protein-coding genes have been associated with development of Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC). Deregulation of non-coding RNAs has been associated with carcinogenesis, but never studied in BE or EAC cells. We used high-resolution methylome analysis to identify changes at genomic regions that encode non-coding RNAs in BE and EAC cells. Methods: We analyzed the methylation status of 1.8 million CpG sites using the massively parallel sequencing-based HELP-tagging assay in matched sets of BE and healthy esophageal tissues from the same patients. We also analyzed human EAC cell lines (OE-33, SK-GT-4, and FLO-1) and human primary non-immortalized esophageal epithelial cells (HEEpiC). Results: BE was characterized by genome-wide loss of methylation that significantly affected intragenic and repetitive elements of the genome. A high proportion of non-coding regions were hypomethylated in BE tissues. The changes in methylation affected small and long non-coding (lnc) regions, and discriminated healthy esophageal from BE tissues, even in matched samples. One lncRNA, AFAP1-AS1, was highly hypomethylated and overexpressed in EAC cells, compared with primary non-malignant esophageal epithelial cells. Knockdown of AFAP1-AS1 with small interfering RNA inhibited proliferation and colony-forming ability of EAC cells, inducing apoptosis; knockdown also significantly reduced EAC cell migration and invasion in Matrigel assays. Conclusions: BE tissues have reduced genome-wide methylation, compared with healthy esophageal tissues, that includes many non-coding regions. Methylation of the long noncoding RNA AFAP1-AS1 is reduced in EAC cells, increasing its expression and the aggressive behavior of cells in culture, similar to activation of protein-coding oncogenes.
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| Overall design |
We did methylation tests for three normal esophagus and three Barrett’s esophagus
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| Contributor(s) |
Wu W, Bhagat T, Amit V, Meltzer SJ |
| Citation missing |
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| Submission date |
Dec 26, 2012 |
| Last update date |
May 15, 2019 |
| Contact name |
Yiting Yu |
| Organization name |
Albert Einstein College of Medicine
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| Street address |
1300 Morris Park Ave
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| City |
Bronx |
| State/province |
NY |
| ZIP/Postal code |
10461 |
| Country |
USA |
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| Platforms (1) |
| GPL9115 |
Illumina Genome Analyzer II (Homo sapiens) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA184727 |
| SRA |
SRP017688 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE43150_RAW.tar |
1.5 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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