Mechanism of miR-222 and miR-126 regulation and its role in asbestos-induced malignancy. (April 2020)

• Record Type: Journal Article
• Authors: Gaetani, Simona; Monaco, Federica; Alessandrini, Federica; Tagliabracci, Adriano; Sabbatini, Armando; Bracci, Massimo; Valentino, Matteo; Neuzil, Jiri; Amati, Monica; Santarelli, Lory; Tomasetti, Marco
• Is Part Of: International journal of biochemistry & cell biology. Volume 121(2020)
• Publication Date: 2020-04
• Subjects: miR-222 -- miR-126 -- Asbestos exposure -- EGFR pathway -- Epigenetic alterations; Biochemistry -- Periodicals; Cytology -- Periodicals; Biochemistry -- Periodicals; Cell Biology -- Periodicals; Biochimie -- Périodiques; Cytologie -- Périodiques; Biochimie; Cytologie; Biochemistry; Cytology; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); Periodicals; 572.05
• DOI: 10.1016/j.biocel.2020.105700
• Languages: English
• ISSNs: 1357-2725

Abstract

Graphical abstract: Highlights: MiR-222 and miR-126 were associated with asbestos exposure and the ensuing malignancy. EGFR pathway and macrophages-induced inflammation resulted in miR-222 upregulation. Asbestos induced miR-126 expression independently of EGFL7 promoter methylation. DNMT1 and PARP1 interact in the regulation of miR-126 expression by chromatin remodelling. DNMT1 negatively correlated with both miR-126 and its host gene EGFL7 in tissues. 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.