miR-186 induces tetraploidy in arsenic exposed human keratinocytes

Cardoso, Ana Paula Ferragut; Nail, Alexandra N.; Banerjee, Minakshi; Wise, Sandra S.; States, J. Christopher

doi:10.1016/j.ecoenv.2023.114823

Cited by 6 publications

(2 citation statements)

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“…It is well known that enhanced cell proliferation due to accelerated cell cycle progression may play key roles in the progression of malignant transformation induced by arsenite [ 38 , 39 ]. Low-dose arsenite can promote the proliferation of a variety of cells [ 12 , 40 , 41 ]. Our research showed that 0.1 μmol/L sodium arsenite, a concentration comparable to human blood arsenic levels found in chronic arsenicosis patients in Inner Mongolia, China [ 42 ], can induce malignant transformation of HaCaT cells.…”

Section: Discussionmentioning

confidence: 99%

“…Abnormal gene transcription has been proposed to address arsenic toxicity and carcinogenicity [ 9 ]. Epigenetic alterations, including differential microRNA (miRNA) expression, have been reported to influence the pathogenesis caused by arsenic via altering some gene expression [ 10 , 11 , 12 ]. MicroRNAs (miRNAs) are endogenous, small, non-coding RNAs consisting of 19–25 nucleotides.…”

Section: Introductionmentioning

confidence: 99%

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MiR-96-5p Suppresses Progression of Arsenite-Induced Human Keratinocyte Proliferation and Malignant Transformation by Targeting Denticleless E3 Ubiquitin Protein Ligase Homolog

Li,

Zhao,

Yao

et al. 2023

Toxics

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Long-term exposure to arsenic has been linked to a variety of cancers, among which skin cancer is the most prevalent form. However, the mechanism underlying arsenic carcinogenesis is unclear, and there is still limited information on the role of miRNAs in arsenic-induced skin cancer. This study aims to explore the role of miR-96-5p in the arsenite-induced proliferation and malignant transformation of human HaCaT keratinocytes. The GEO database (accession numbers GSE97303, GSE97305, and GSE97306) was used to extract mRNA and miRNA expression profiles of HaCaT cells treated with or without 0.1 μmol/L sodium arsenite for 3 and 7 weeks. In this paper, according to the CCK8 assay result, HaCaT cells exposed to 0.1 μmol/L sodium arsenite for 48 h were finalized. CCK8, MTT, EdU incorporation, and colony formation assays were used to determine the viability and proliferation of HaCaT cells and transformed HaCaT (T-HaCaT) cells. The subcellular localization and relative expression levels of DTL, as well as miR-96-5p in HaCaT cells induced by arsenite, were determined via immunofluorescence, RT-qPCR, and Western blot. Dual-luciferase reporter assay was performed to identify miR-96-5p bound directly to DTL. Transfection of miR-96-5p mimics or DTL siRNA was conducted to verify the arsenite-induced viability of HaCaT cells and T-HaCaT cells. T-HaCaT cells and nude mice were used to construct arsenite-induced malignant transformation and an in vivo xenograft model to demonstrate the over-expressed effect of miR-96-5p. The results showed that DTL was the target gene of miR-96-5p. Meanwhile, we also found that 0.1 μmol/L sodium arsenite upregulated DTL by decreasing the miR-96-5p level, leading to the proliferation and malignant transformation of HaCaT cells. MiR-96-5p agomir treatment slowed the growth of transplanted HaCaT cells transformed by arsenite in a manner associated with DTL downregulation in the nude mice xenograft model. Taken together, we confirmed that miR-96-5p, as a potent regulator of DTL, suppressed arsenite-induced HaCaT cell proliferation and malignant transformation, which might provide a novel therapeutic target for the treatment of arsenic-induced skin cancer.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

MiR-96-5p Suppresses Progression of Arsenite-Induced Human Keratinocyte Proliferation and Malignant Transformation by Targeting Denticleless E3 Ubiquitin Protein Ligase Homolog

Li,

Zhao,

Yao

et al. 2023

Toxics

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Mechanisms of genotoxicity and proteotoxicity induced by the metalloids arsenic and antimony

Wysocki,

Rodrigues,

Litwin

et al. 2023

Cell. Mol. Life Sci.

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Arsenic and antimony are metalloids with profound effects on biological systems and human health. Both elements are toxic to cells and organisms, and exposure is associated with several pathological conditions including cancer and neurodegenerative disorders. At the same time, arsenic- and antimony-containing compounds are used in the treatment of multiple diseases. Although these metalloids can both cause and cure disease, their modes of molecular action are incompletely understood. The past decades have seen major advances in our understanding of arsenic and antimony toxicity, emphasizing genotoxicity and proteotoxicity as key contributors to pathogenesis. In this review, we highlight mechanisms by which arsenic and antimony cause toxicity, focusing on their genotoxic and proteotoxic effects. The mechanisms used by cells to maintain proteostasis during metalloid exposure are also described. Furthermore, we address how metalloid-induced proteotoxicity may promote neurodegenerative disease and how genotoxicity and proteotoxicity may be interrelated and together contribute to proteinopathies. A deeper understanding of cellular toxicity and response mechanisms and their links to pathogenesis may promote the development of strategies for both disease prevention and treatment.

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