Methylomic analysis identifies C11orf87 as a novel epigenetic biomarker for GI cancers

Autor: Kun-Tu Yeh, Himani Kumari, Jie-Ting Low, Yu-Ming Chuang, Yin-Chen Chen, Yu-Ting Lee, Shu-Hui Lin, Wan-Hong Huang, Hongchuan Jin, Mita T. M. T. Tran, Po-Yen Hsu, Michael W.Y. Chan
Rok vydání: 2020
Předmět:
Male
Microarrays
Biochemistry
Epigenesis
Genetic
Epigenome
Medicine and Health Sciences
Promoter Regions
Genetic
Gastrointestinal Neoplasms
Aged
80 and over
Multidisciplinary
DNA methylation
Liver Diseases
Chemical Reactions
Methylation
Esophageal cancer
Middle Aged
Prognosis
Chromatin
Nucleic acids
Chemistry
Bioassays and Physiological Analysis
Oncology
Physical Sciences
Medicine
Biomarker (medicine)
Female
Epigenetics
DNA modification
Chromatin modification
Research Article
Chromosome biology
Adult
STAT3 Transcription Factor
Cell biology
Esophageal Cancer
Science
Gastroenterology and Hepatology
Research and Analysis Methods
Disease-Free Survival
Causes of cancer
Open Reading Frames
Cell Line
Tumor
Gastrointestinal Tumors
medicine
Biomarkers
Tumor
Genetics
Humans
Aged
Biology and life sciences
business.industry
Carcinoma
Cancer
Cancers and Neoplasms
DNA
Hepatocellular Carcinoma
medicine.disease
Gastric Cancer
Head and Neck Cancers
Cancer research
Ectopic expression
Gene expression
business
Biomarkers
Zdroj: PLoS ONE
PLoS ONE, Vol 16, Iss 4, p e0250499 (2021)
ISSN: 1932-6203
Popis: Gastric cancer is one of the leading causes of cancer death worldwide. Previous studies demonstrated that activation of STAT3 is crucial for the development and progression of gastric cancer. However, the role of STAT3 in neuronal related gene methylation in gastric cancer has never been explored. In this study, by using DNA methylation microarray, we identified a potential STAT3 target, C11orf87, showing promoter hypomethylation in gastric cancer patients with lower STAT3 activation and AGS gastric cancer cell lines depleted with STAT3 activation. Although C11orf87 methylation is independent of its expression, ectopic expression of a constitutive activated STAT3 mutant upregulated its expression in gastric cancer cell line. Further bisulfite pyrosequencing demonstrated a progressive increase in DNA methylation of this target in patient tissues from gastritis, intestinal metaplasia, to gastric cancer. Intriguingly, patients with higher C11orf87 methylation was associated with better survival. Furthermore, hypermethylation of C11orf87 was also frequently observed in other GI cancers, as compared to their adjacent normal tissues. These results suggested that C11orf87 methylation may serve as a biomarker for diagnosis and prognosis of GI cancers, including gastric cancer. We further postulated that constitutive activation of STAT3 might be able to epigenetically silence C11orf87 as a possible negative feedback mechanism to protect the cells from the overactivation of STAT3. Targeted inhibition of STAT3 may not be appropriate in gastric cancer patients with promoter hypermethylation of C11orf87.
Databáze: OpenAIRE
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