Mechanism of miR-222 and miR-126 regulation and its role in asbestos-induced malignancy

0535309 - BTÚ 2021 RIV GB eng J - Článek v odborném periodiku
Gaetani, S. - Monaco, F. - Alessandrini, F. - Tagliabracci, A. - Sabbatini, A. - Bracci, M. - Valentino, M. - Neužil, Jiří - Amati, M. - Santarelli, L. - Tomasetti, M.
Mechanism of miR-222 and miR-126 regulation and its role in asbestos-induced malignancy.
International Journal of Biochemistry and Cell Biology. Roč. 121, APR 2020 (2020), č. článku 105700. ISSN 1357-2725. E-ISSN 1878-5875
Grant CEP: GA MZd(CZ) NV16-31604A
Institucionální podpora: RVO:86652036
Klíčová slova: host gene egfl7 * dna methylation * cancer * miR-222
Obor OECD: Biochemistry and molecular biology
Impakt faktor: 5.085, rok: 2020
Způsob publikování: Open access
https://www.sciencedirect.com/science/article/pii/S1357272520300170?via%3Dihub

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 down regulated 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.
Trvalý link: http://hdl.handle.net/11104/0313411