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Upregulation of microRNA-4417 and Its Target Genes Contribute to Nickel Chloride-promoted Lung Epithelial Cell Fibrogenesis and Tumorigenesis
- Source :
- Scientific Reports, Scientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
- Publication Year :
- 2017
- Publisher :
- Springer Science and Business Media LLC, 2017.
-
Abstract
- Nickel compounds have been classified as carcinogens and shown to be associated with induction of epithelial-mesenchymal transition (EMT) in fibrogenesis and tumorigenesis, as well as the crucial role of microRNAs (miRNAs) and their related genes in controlling EMT and cancer metastasis. Thus, the mechanisms involved in the regulation of EMT in nickel-treated cells are of potential interest in understanding lung fibrosis and tumor progression. We investigated the miRNA-dependent mechanisms involved in nickel-induced EMT in lung epithelial cells. Nickel increased miR-4417 expression and decreased its target gene TAB2 expression. Treatment of cells with TGF-β inhibitor SB525334 significantly blocked NiCl2 and TGF-β-induced EMT. The expression of miR-4417 was abolished by SB525334 in TGF-β-treated cells, but not in nickel-treated cells. Both overexpression of miR-4417 and silencing of TAB2 induced fibronectin expression, but did not reduce E-cadherin expression. Moreover, oral administration of nickel promoted lung tumor growth in nude mice that had received BEAS-2B transformed cells by intravenous injection. The induction of EMT by nickel is mediated through multiple pathways. Induction of abundant miR-4417 and reduction of TAB2 expression following nickel exposure and may be involved in nickel-induced fibronectin. These findings provide novel insight into the roles of nickel in fibrogenesis and tumor progression.
- Subjects :
- inorganic chemicals
0301 basic medicine
Lung Neoplasms
Pulmonary Fibrosis
lcsh:Medicine
Respiratory Mucosa
medicine.disease_cause
Article
03 medical and health sciences
0302 clinical medicine
Downregulation and upregulation
Nickel
microRNA
otorhinolaryngologic diseases
medicine
Humans
Gene silencing
RNA, Neoplasm
lcsh:Science
Lung
Carcinogen
Cell Line, Transformed
Multidisciplinary
biology
Chemistry
lcsh:R
Epithelial Cells
Fibronectin
MicroRNAs
Cell Transformation, Neoplastic
030104 developmental biology
Cell culture
Tumor progression
030220 oncology & carcinogenesis
Cancer research
biology.protein
lcsh:Q
Carcinogenesis
Subjects
Details
- ISSN :
- 20452322
- Volume :
- 7
- Database :
- OpenAIRE
- Journal :
- Scientific Reports
- Accession number :
- edsair.doi.dedup.....9e113abaf9ca8fa76de5d002bbafd496