Association between urinary arsenic metabolites and dicer expression in occupational arsenic-exposed workers and the role of dicer in cell proliferation

JIANG Cheng-lan; LI Shu-ting; JIANG Jin-yun; YANG Xue-fei; LU Da-yan; HE Yue-feng

PDF(1427 KB)

China Environmental Science ›› 2025, Vol. 45 ›› Issue (5) : 2905-2912.

Environmental Toxicology and Environmental Health

Association between urinary arsenic metabolites and dicer expression in occupational arsenic-exposed workers and the role of dicer in cell proliferation

JIANG Cheng-lan, LI Shu-ting, JIANG Jin-yun, YANG Xue-fei, LU Da-yan, HE Yue-feng

Author information +

History +

Abstract

This study investigated the relationship between Dicer expression levels and urinary arsenic metabolites both in vivo and in vitro, as well as examined the role of Dicer in cell proliferation. For the epidemiological analysis, workers from a high arsenic-polluted factory in Yunnan Province were selected as the arsenic-exposed group, while residents from nearby villages without arsenic exposure history were recruited as controls. Urinary arsenic species (inorganic arsenic, monomethylarsonic acid [MMA], and dimethylarsinic acid [DMA]) were quantified, and Dicer mRNA expression levels in peripheral blood were measured. It was found that the relative Dicer mRNA expression in the arsenic-exposed group was significantly elevated compared to controls. Furthermore, Dicer mRNA levels were positively correlated with urinary inorganic arsenic, MMA, and DMA concentrations. For in vitro experiments, human bronchial epithelial cells (16HBE) were treated with sodium arsenite (1.5, 3, 4.5μmol/L) or 4.5μmol/L MMA, DMA, or sodium arsenite. Dicer mRNA and protein expression were analyzed by RT-qPCR and Western blot. Additionally, Dicer expression was knocked down in 16HBE cells using siRNA, and cell viability and proliferation were assessed via CCK-8 and EdU assays. It was observed that Dicer mRNA and protein levels in 3 and 4.5μmol/L sodium arsenite-treated cells were significantly upregulated compared to untreated controls, whereas no changes were detected in MMA- or DMA-treated groups. Knockdown of Dicer was shown to suppress cell viability and proliferation. Notably, sodium arsenite exposure combined with Dicer knockdown resulted in a more pronounced reduction in cell proliferation rates.

Key words

16HBE cells / Dicer / occupational arsenic exposure / proliferation

Cite this article

EndNote

Ris (Procite)

Bibtex

Download Citations

JIANG Cheng-lan, LI Shu-ting, JIANG Jin-yun, YANG Xue-fei, LU Da-yan, HE Yue-feng. Association between urinary arsenic metabolites and dicer expression in occupational arsenic-exposed workers and the role of dicer in cell proliferation[J]. China Environmental Science. 2025, 45(5): 2905-2912

References

[1] Nurchi V M, Djordjevic A B, Crisponi G, et al. Arsenic toxicity: Molecular targets and therapeutic agents[J]. Biomolecules, 2020,10(2): 235.
[2] Pershagen G. Lung cancer mortality among men living near an arsenic-emitting smelter[J]. American Journal of Epidemiology, 1985, 122:684-694.
[3] De Gregori I, Fuentes E, Rojas M, et al. Monitoring of copper, arsenic and antimony levels in agricultural soils impacted and non-impacted by mining activities, from three regions in Chile[J]. Journal of Environmental Monitoring, 2003,5:287-295.
[4] Sassano M, Seyyedsalehi Ms, Siea Ac, et al. Occupational arsenic exposure and digestive and head and neck cancers: A systematic review and meta-analysis[J]. Environmental Research, 2024,260: 119643.
[5] Folesani G, Galetti M, Petronini Pg, et al. Interaction between occupational and non-occupational arsenic exposure and tobacco smoke on lung cancerogenesis: A systematic review[J]. International Journal of Environmental Research and Public Health, 2023,20(5): 4167.
[6] Román M D, Niclis C, Aballay L R, et al. Do Exposure to arsenic, occupation and diet have synergistic effects on prostate cancer risk?[J]. Asian Pacific Journal of Cancer Prevention, 2018,19:1495-1501.
[7] Di Leva G, Garofalo M, Croce C M. MicroRNAs in cancer[J]. Annual Review of Pathology, 2014,9:287-314.
[8] Zapletal D, Kubicek K, Svoboda P, et al. Dicer structure and function: conserved and evolving features[J]. EMBO Reports, 2023,24(7): e57215.
[9] Vergani-Junior C A, Tonon-Da-Silva G, Inan M D, et al. DICER: structure, function, and regulation[J]. Biophysical Reviews, 2021, 13(6):1081-1090.
[10] Tseng C F, Chen L T, Wang H D, et al. Transcriptional suppression of Dicer by HOXB-AS3/EZH2 complex dictates sorafenib resistance and cancer stemness[J]. Cancer Science, 2022,113(5):1601-1612.
[11] Shan W, Sun C, Zhou B, et al. Role of Dicer as a prognostic predictor for survival in cancer patients: a systematic review with a meta-analysis[J]. Oncotarget, 2016,7(45):72672-72684.
[12] Zhao H, Jin X, Su H, et al. Down-regulation of Dicer expression in cervical cancer tissues[J]. Medical Oncology, 2014,31(5):937.
[13] Yu J, Li S, Shen S, et al. The transcript NR 134251.1of lncRNA APTR with an opposite function to all transcripts inhibits proliferation and induces apoptosis by regulating proliferation and apoptosis-related genes[J]. Human& Experimental Toxicology, 2023;42: 9603271221150247.
[14] Rager Je, Yosim A, Fry Rc. Prenatal exposure to arsenic and cadmium impacts infectious disease-related genes within the glucocorticoid receptor signal transduction pathway[J]. International Journal of Molecular Sciences, 2014,15(12):22374-22391.
[15] Shimoda Y, Kato K, Asami S, et al. Differences in apoptotic signaling and toxicity between dimethylmonothioarsinic acid (DMMTAV) and its active metabolite, dimethylarsinous acid (DMAIII), in HepaRG cells: Possibility of apoptosis cascade based on diversity of active metabolites of DMMTAV[J]. Journal of Trace Elements in Medicine and Biology, 2018,50:188-197.
[16] Suzuki T, Yamashita S, Ushijima T, et al. Genome-wide analysis of DNA methylation changes induced by gestational arsenic exposure in liver tumors[J]. Cancer Science, 2013,104(12):1575-1585.
[17] Sun M, Cheng H, Yu T, et al. Involvement of a AS3MT/c-Fos/ p53signaling axis in arsenic-induced tumor in human lung cells[J]. Environmental Toxicology, 2023,38(3):615-627.
[18] Wang X, Chen H, Wen Y, et al. Dicer affects cisplatin-mediated apoptosis in epithelial ovarian cancer cells[J]. Molecular Medicine Reports, 2018,18(5):4381-4387.
[19] Su Cm, Hsu Tw, Chen Ha, et al. Chaperone-mediated autophagy degrade Dicer to promote breast cancer metastasis[J]. Cellular Physiology, 2023,238(4):829-841.
[20] Faber C, Horst D, Hlubek F, et al. Overexpression of Dicer predicts poor survival in colorectal cancer[J]. European Journal of Cancer, 2011,47(9):1414-1419.
[21] Chiosea S, Jelezcova E, Chandran U, et al. Up-regulation of dicer, a component of the MicroRNA machinery, in prostate adenocarcinoma[J]. The American Journal of Pathology, 2006,169(5):1812-1820.
[22] Bakir M B, Salama M A, Refaat R, et al. Evaluating the therapeutic potential of one-carbon donors in nonalcoholic fatty liver disease[J]. European Journal of Pharmacology, 2019,847:72-82.
[23] Deshpande A A, Bhatia M, Laxman S, et al. Thiol trapping and metabolic redistribution of sulfur metabolites enable cells to overcome cysteine overload[J]. Microbial Cell, 2017,4(4):112-126.
[24] Kuo C C, Moon K A, Wang S L, et al. The association of arsenic metabolism with cancer, cardiovascular disease, and diabetes: A systematic review of the epidemiological evidence[J]. Environmental Health Perspectives, 2017,125(8):087001.
[25] Tan J, Sun M, Luo Q, et al. Arsenic exposure increased expression of HOTAIR and LincRNA-p21 in vivo and vitro[J]. Environmental Science and Pollution Research International, 2021,28(1):587-596.
[26] Wang M, Tan J, Jiang C, et al. Inorganic arsenic influences cell apoptosis by regulating the expression of MEG3 gene[J]. Environmental Geochemistry and Health, 2021,43(1):475-484.
[27] Mudhasani R, Zhu Z, Hutvagner G, et al. Loss of miRNA biogenesis induces p19Arf-p53signaling and senescence in primary cells[J]. The Journal of Cell Biology, 2008,181(7):1055-1063.
[28] Harris K S, Zhang Z, Mcmanus M T, et al. Dicer function is essential for lung epithelium morphogenesis[J]. Proceedings of the National Academy of Sciences of the United States of America, 2006,103(7): 2208-2213.
[29] Roche B, Arcangioli B, Martienssen R. New roles for Dicer in the nucleolus and its relevance to cancer[J]. Cell Cycle, 2017,16(18): 1643-1653.