Mechanism of miR-222 and miR-126 regulation and its role in asbestos-induced malignancy
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Monaco, Federica
Alessandrini, Federica
Tagliabracci, Adriano
Sabbatini, Armando
Bracci, Massimo
Valentino, Matteo
Neuzil, Jiri
Amati, Monica
Santarelli, Lory
Tomasetti, Marco
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Abstract
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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The International Journal of Biochemistry & Cell Biology
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121
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Biochemistry and cell biology
Medical biochemistry and metabolomics
Medical physiology
Science & Technology
Life Sciences & Biomedicine
Biochemistry & Molecular Biology
Cell Biology
miR-222
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Gaetani, S; Monaco, F; Alessandrini, F; Tagliabracci, A; Sabbatini, A; Bracci, M; Valentino, M; Neuzil, J; Amati, M; Santarelli, L; Tomasetti, M, Mechanism of miR-222 and miR-126 regulation and its role in asbestos-induced malignancy, The International Journal of Biochemistry & Cell Biology, 2020, 121, pp. 105700