Mechanism of miR-222 and miR-126 regulation and its role in asbestos-induced malignancy
Language English Country Netherlands Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
32006662
DOI
10.1016/j.biocel.2020.105700
PII: S1357-2725(20)30017-0
Knihovny.cz E-resources
- Keywords
- Asbestos exposure, EGFR pathway, Epigenetic alterations, miR-126, miR-222,
- MeSH
- Asbestos adverse effects MeSH
- Carcinogens chemistry MeSH
- Humans MeSH
- Mesothelioma, Malignant MeSH
- Mesothelioma genetics pathology MeSH
- MicroRNAs metabolism MeSH
- Lung Neoplasms genetics pathology MeSH
- Aged MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Aged MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Asbestos MeSH
- Carcinogens MeSH
- MicroRNAs MeSH
- MIRN126 microRNA, human MeSH Browser
- MIRN222 microRNA, human MeSH Browser
MiR-222 and miR-126 are associated with asbestos exposure and the ensuing malignancy, but the mechanism(s) of their regulation remain unclear. We evaluated the mechanism by which asbestos regulates miR-222 and miR-126 expression in the context of cancer etiology. An 'in vitro' model of carcinogen-induced cell transformation was used based on exposing bronchial epithelium BEAS-2B cells to three different carcinogens including asbestos. Involvement of the EGFR pathway and the role of epigenetics have been investigated in carcinogen-transformed cells and in malignant mesothelioma, a neoplastic disease associated with asbestos exposure. Increased expression of miR-222 and miR-126 were found in asbestos-transformed cells, but not in cells exposed to arsenic and chrome. Asbestos-mediated activation of the EGFR pathway and macrophages-induced inflammation resulted in miR-222 upregulation, which was reversed by EGFR inhibition. Conversely, asbestos-induced miR-126 expression was affected neither by EGFR modulation nor inflammation. Rather than methylation of the miR-126 host gene EGFL7, epigenetic mechanism involving DNMT1- and PARP1-mediated chromatin remodeling was found to upregulate of miR-126 in asbestos-exposed cells, while miR-126 was downregulated in malignant cells. Analysis of MM tissue supported the role of PARP1 in miR-126 regulation. Therefore, activation of the EGFR pathway and the PARP1-mediated epigenetic regulation both play a role in asbestos-induced miRNA expression, associated with in asbestos-induced carcinogenesis and tumor progression.
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