Promoter hypermethylation of the <i>CFTR</i> gene and clinical/pathological features associated with non‐small cell lung cancer

Son, Ji Woong; Kim, Young Jin; Cho, Hyun Min; Lee, Soo Young; Lee, Su Man; Kang, Jaeku; Lee, Jung Uee; Lee, Yu Mi; Kwon, Sun Jung; Choi, Eugene; Na, Moon Jun; Park, Jae Yong; Kim, Dong Sun

doi:10.1111/j.1440-1843.2011.01994.x

Cited by 57 publications

(63 citation statements)

References 35 publications

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“…We propose that ion channels/transporters located at the cell surface may function as epigenetic regulators by sensing environmental changes and transducing the micro-environmental signals into miRNA alteration, which subsequently leads to cellular adaptive responses in health and disease. To this end, ion channels have been reported to be associated with other epigenetic mechanisms apart from miRNAs, such as DNA methylation [74] and histone modification [75], reinforcing the importance of these molecules in the regulation of a wide variety of biological processes. Considering the fact that epigenetic research is paving the way for many new breakthroughs in the prevention, diagnosis and treatment of human diseases, focused efforts on the detailed mechanisms linking the environment and epigenetic responses in physiological/pathological conditions have an immense potential in improving human health and welfare.…”

Section: Conclusion and Perspectivementioning

confidence: 99%

Ion channels/transporters as epigenetic regulators? —a microRNA perspective

Jiang

Zhang

Chan

2012

Sci. China Life Sci.

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MicroRNA (miRNA) alterations in response to changes in an extracellular microenvironment have been observed and considered as one of the major mechanisms for epigenetic modifications of the cell. While enormous efforts have been made in the understanding of the role of miRNAs in regulating cellular responses to the microenvironment, the mechanistic insight into how extracellular signals can be transduced into miRNA alterations in cells is still lacking. Interestingly, recent studies have shown that ion channels/transporters, which are known to conduct or transport ions across the cell membrane, also exhibit changes in levels of expression and activities in response to changes of extracellular microenvironment. More importantly, alterations in expression and function of ion channels/transporters have been shown to result in changes in miRNAs that are known to change in response to alteration of the microenvironment. In this review, we aim to summarize the recent data demonstrating the ability of ion channels/transporters to transduce extracellular signals into miRNA changes and propose a potential link between cells and their microenvironment through ion channels/transporters. At the same time, we hope to provide new insights into epigenetic regulatory mechanisms underlying a number of physiological and pathological processes, including embryo development and cancer metastasis. ion channel, miRNAs, epigenetic, microenvironment

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Section: Conclusion and Perspectivementioning

confidence: 99%

Ion channels/transporters as epigenetic regulators? —a microRNA perspective

Jiang

Zhang

Chan

2012

Sci. China Life Sci.

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“…29 Interestingly, the CFTR promoter was hypermethylated in cancer tissues of endodermic origin. [15][16][17] Also of note, genes associated with bivalent chromatin in ES cells are prone to acquiring DNA methylation during aging. 30 Based upon these findings, we suggest that the progressive decline of the pulmonary function in cystic fibrosis patients is, at least partly, a consequence of CFTR methylation in bronchial epithelial cells.…”

Section: Discussionmentioning

confidence: 99%

“…The promoter of CFTR is highly methylated in lung, liver, and bladder cancers, showing that the gene may acquire DNA methylation during cell transformation. [15][16][17] Moreover, most of the factors that either activate or repress CFTR transcription are associated with HATs (Histone acetyltransferases) and HDACs (Histone deacetylases), respectively. 7,18 Since epigenetic modifications are profoundly altered by cell culture, we addressed the regulation of CFTR in a physiological context by analyzing human tissues from non-cystic fibrosis donors.…”

Section: Introductionmentioning

confidence: 99%

A balance between activating and repressive histone modifications regulatescystic fibrosis transmembrane conductance regulator (CFTR) expression in vivo

et al. 2014

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“…The in vivo and in vitro experiments present knockdown of CFTR promotes epithelial-mesenchymal transition, invasion and migration of NSCLC cells; conversely, overexpression of CFTR suppresses cancer progression of NSCLC (22). Methylation of the CFTR gene is significantly greater in lung SCC than in lung adenocarcinomas and CFTR gene methylation is associated with significantly poorer survival in young patients, but not in elderly patients (30). Based on the above, low expression of CFTR might play pivotal roles in the process of lung SCC metastasis.…”

Section: Discussionmentioning

confidence: 99%

Weighted gene co-expression network analysis in identification of metastasis-related genes of lung squamous cell carcinoma based on the Cancer Genome Atlas database

Tian¹,

Zhao²,

Xiu³

et al. 2017

J. Thorac. Dis.

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Background: Lung squamous cell carcinoma (lung SCC) is a common type of malignancy. Its pathogenesis mechanism of tumor development is unclear. The aim of this study was to identify key genes for diagnosis biomarkers in lung SCC metastasis. Methods: We searched and downloaded mRNA expression data and clinical data from The Cancer Genome Atlas (TCGA) database to identify differences in mRNA expression of primary tumor tissues from lung SCC with and without metastasis. Gene co-expression network analysis, protein-protein interaction (PPI) network, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and quantitative real-time polymerase chain reactions (qRT-PCR) were used to explore the biological functions of the identified dysregulated genes.Results: Four hundred and eighty-two differentially expressed genes (DEGs) were identified between lung SCC with and without metastasis. Nineteen modules were identified in lung SCC through weighted gene co-expression network analysis (WGCNA). Twenty-three DEGs and 26 DEGs were significantly enriched in the respective pink and black module. KEGG pathway analysis displayed that 26 DEGs in the black module were significantly enriched in bile secretion pathway. Forty-nine DEGs in the two gene co-expression module were used to construct PPI network. CFTR in the black module was the hub protein, had the connectivity with 182 genes. The results of qRT-PCR displayed that FIGF, SFTPD, DYNLRB2 were significantly down-regulated in the tumor samples of lung SCC with metastasis and CFTR, SCGB3A2, SSTR1, SCTR, ROPN1L had the down-regulation tendency in lung SCC with metastasis compared to lung SCC without metastasis. Conclusions: The dysregulated genes including CFTR, SCTR and FIGF might be involved in the pathology of lung SCC metastasis and could be used as potential diagnosis biomarkers or therapeutic targets for lung SCC. IntroductionLung squamous cell carcinoma (lung SCC) is a histological subtype of non-small cell lung cancer (NSCLC), which is the second most frequent type of NSCLC after lung adenocarcinoma (1). Lung SCC is a multi-step progressive disease with high rates of morbidity and mortality worldwide.The initiation of lung SCC is divided into the following five successive stages: normal bronchial epithelium, squamous metaplasia, mild-moderate dysplasia, carcinoma in situ, and invasive carcinoma (2). The prognosis of lung cancer is unfavorable, despite significant therapeutic improvements have been made in recent years. In current, there is no specific molecular targets for therapy have been identified (3), therefore, cisplatin plus gemcitabine is still the first-line treatment for lung SCC (4).Currently, the tumorigenesis mechanism of lung SCC remains unclear. Numerous published articles demonstrate that dysregulated genes are essential for initiation, progression and development of lung cancer. SMC4 (structural maintenance of chromosome 4) is over-expressed in lung adenocarcinoma tissues and its inhibition significantly suppresses the prolif...

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Promoter hypermethylation of the CFTR gene and clinical/pathological features associated with non‐small cell lung cancer

Abstract: These findings suggest that DNA methylation may be important for downregulation of CFTR gene expression in lung cancer. Promoter hypermethylation of the CFTR gene may be an important prognostic factor in younger patients with NSCLC.

Cited by 57 publications

References 35 publications

Ion channels/transporters as epigenetic regulators? —a microRNA perspective

Ion channels/transporters as epigenetic regulators? —a microRNA perspective

A balance between activating and repressive histone modifications regulatescystic fibrosis transmembrane conductance regulator (CFTR) expression in vivo

Weighted gene co-expression network analysis in identification of metastasis-related genes of lung squamous cell carcinoma based on the Cancer Genome Atlas database

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