Abstract |
Chronic arsenic exposure through drinking water is a global health issue, affecting >200 million people. Arsenic is a group I human carcinogen and causes chromosomal instability (CIN). Arsenic exposure is the second most common cause of skin cancer after UV radiation. hsa-miR-186 is overexpressed in arsenic-induced squamous cell carcinoma relative to premalignant hyperkeratosis. Among predicted targets of hsa-miR-186 are cell cycle regulators including regulators of mitotic progression. Disruption of mitotic progression can contribute to CIN. Thus, we hypothesized that hsa-miR-186 overexpression contributes to malignant transformation of arsenic exposed HaCaT cells by induction of CIN. Stable clones of HaCaT cells transfected with pEP-hsa-miR-186 expression vector or empty vector were maintained under puromycin selection and exposed to 0 or 100 nM NaAsO2 and cultured for 29 weeks. HaCaT clones overexpressing hsa-miR-186 and exposed to NaAsO2 showed increased CIN and anchorage independent growth at 29 weeks in a stochastic manner, in contrast to unexposed empty vector transfected clones. These results suggest that clonal variability mediates arsenic-induced carcinogenesis in hsa-miR-186 overexpressing human keratinocytes.
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Authors | Angeliki Lykoudi, Ana P Ferragut Cardoso, Sandra S Wise, Mayukh Banerjee, J Christopher States |
Journal | Toxicology and applied pharmacology
(Toxicol Appl Pharmacol)
Vol. 479
Pg. 116730
(Nov 15 2023)
ISSN: 1096-0333 [Electronic] United States |
PMID | 37866707
(Publication Type: Journal Article)
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Copyright | Copyright © 2023. Published by Elsevier Inc. |
Chemical References |
- MIRN186 microRNA, human
- Arsenic
- MicroRNAs
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Topics |
- Humans
- Arsenic
(toxicity, metabolism)
- Cell Line
- MicroRNAs
(genetics, metabolism)
- Carcinogenesis
(genetics)
- Keratinocytes
(metabolism)
- Clone Cells
- Phenotype
- Chromosomal Instability
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