ALDH3A1通过IL-6/STAT3信号通路激活GMA诱导的恶性转化16HBE细胞上皮间充质转化

doi:10.3969/j.issn.1004-616x.2023.06.001

Abstract

Abstract: OBJECTIVE：As a carcinogen classified as Group 2A by the International Agency for Research on Cancer (IARC)，glycidyl methacrylate (GMA) is widely used in the synthesis and modification of various composite materials. However，the specific carcinogenic mechanism of GMA remains unclear. This study aimed to investigate whether the key molecular mechanisms underlying the malignant transformation of 16HBE cells induced by GMA are associated with the expression of aldehyde dehydrogenase 3A1 (ALDH3A1). METHODS：The transient transfection technique was used to overexpress ALDH3A1 in the GMA-induced malignant transformed 16HBE cells，which was established by our research group in previous work. qPCR and Western blot techniques were used to analyze the gene and protein expression levels of IL-6/signal transducer and activator of transcription 3 (STAT3) pathway and epithelial-mesenchymal transition (EMT) markers，including E-cadherin，Vimentin，matrix metalloproteinase 3 (MMP3) and Snail protein and mRNA expression. RESULTS：The qPCR and Western blot results showed that，compared to the control group，the ALDH3A1 overexpression group upregulation of E-cadherin expression，and downregulation of IL-6，STAT3，p-STAT3，MMP3 and Snail expression (P<0.05). Additionally，the transcription levels of MMP3，Snail，and Vimentin were downregulated (P<0.05). The results indicated that ALDH3A1 reduced the expression of several key proteins involved in the EMT process in GMA-induced malignant transformed 16HBE cells by inhibiting the activation of the IL6/STAT3 pathway. CONCLUSION：ALDH3A1 is closely associated with the GMA-induced malignant transformation process in 16HBE cells，and it inhibits the activation of the IL-6/STAT3 pathway，thereby attenuating the expression of multiple key proteins involved in the EMT process. These findings contribute to elucidating the carcinogenic mechanism of GMA and provide potential biomarkers for the assessment of health effects of GMA exposure.

Key words: glycidyl methacrylate, 16HBE cells, ALDH3A1, epithelial-mesenchymal transition, IL-6/STAT3 signalling pathway

CLC Number:

R730.2

WANG Quankai, JIN Huiping, LI Xinwei, CUI Xufang, GU Yiting, WUHAN Baolier, KANG Tongying, XU Jianning. ALDH3A1 activates GMA-induced malignant transformation of epithelial mesenchymal transition in 16HBE cells via the IL-6/STAT3 signalling pathway[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2023, 35(6): 405-411.

References

[1] XIAO N, CAO H B, CHEN C H, et al. A novel aldehyde dehydrogenase-3 activator (Alda-89) protects submandibular gland function from irradiation without accelerating tumor growth[J]. Clin Cancer Res, 2013, 19(16):4455-4464.
[2] OECD, 2009. The 2007 OECD list of high production volume chemicals. OECD Environment, Health and Safety Publications, Series on Testing and Assessment:No. 112[EB/OL].(2009-10-23). https://one.oecd.org/document/ENV/JM/MONO(2009)40/en/pdf.
[3] OECD-SIDS, 2000. Glycidyl methacrylate. SIDS Initial Assessment Report for the 10th SIAM[R/OL]. (2000-05-15). https://hpvchemicals.oecd.org/ui/handler.axd-id=44D6C34E-1889-4EFD-A534-47AE7B2986F5.
[4] BATIONO R, JORDANA F, BOILEAU M J, et al. Release of monomers from orthodontic adhesives[J]. Am J Orthod Dentofacial Orthop, 2016, 150(3):491-498.
[5] IARC MONOGRAPHS VOL GROUP. Carcinogenicity of some industrial chemical intermediates and solvents[J]. Lancet Oncol, 2020, 21(1):25-26.
[6] YANG M, XU J N, WANG Q K, et al. Study on malignant transformation of human bronchial epithelial cells induced by glycidyl methacrylate[J]. Chin J Prev Med, 2009, 43(3):187-192.
[7] QU Y, HE Y, YANG Y, et al. ALDH3A1 acts as a prognostic biomarker and inhibits the epithelial mesenchymal transition of oral squamous cell carcinoma through IL-6/STAT3 signaling pathway[J]. J Cancer, 2020, 11(9):2621-2631.
[8] PATEL M, LU L, ZANDER D S, et al. ALDH1A1 and ALDH3A1 expression in lung cancers:correlation with histologic type and potential precursors[J]. Lung Cancer, 2008, 59(3):340-349.
[9] FAN F F, YIN R X, WANG L Y, et al. ALDH3A1 driving tumor metastasis is mediated by p53/BAG1 in lung adenocarcinoma[J]. J Cancer, 2021, 12(16):4780-4790.
[10] WANG B Y, HE Y, WANG B, et al. ALDH3A1 overexpression in OSCC inhibits inflammation via phospho-Ser727 at STAT3 in tumor-associated macrophages[J]. Oral Dis, 2023, 29(4):1513-1524.
[11] 杨敏, 许建宁, 王全凯, 等. 甲基丙烯酸环氧丙酯致人支气管上皮细胞恶性转化研究[J]. 中华预防医学杂志, 2009, 43(3):187-192.
[12] LI X W, WANG Q K, WANG M, et al. TMT-based quantitative proteomic analysis reveals the underlying mechanisms of glycidyl methacrylate-induced 16HBE cell malignant transformation[J]. Toxicology, 2023, 485:153427.
[13] HEIDELBERGER C. Chemical carcinogenesis[J]. Cancer, 1977, 40(1 Suppl):430-433.
[14] 欧阳国顺, 郝爱功, 樊仲讷, 等. 甲基丙烯酸甲酯的亚急性毒性致突变性和致畸性[J]. 中华劳动卫生职业病杂志, 1989, 7(2):80-81.
[15] 杨俊保, 李忠生, 许建宁, 等. 甲基丙烯酸环氧丙酯对金仓鼠胚胎细胞的转化作用[J]. 卫生研究, 1996, 25(5):261-264.
[16] 张淑琪, 许建宁, 徐凤丹, 等. 甲基丙烯酸环氧丙酯对BALB/c 3T3细胞恶性转化的实验研究[J]. 卫生研究, 1996, 25(3):129-133.
[17] BLACK W J, STAGOS D, MARCHITTI S A, et al. Human aldehyde dehydrogenase genes:alternatively spliced transcriptional variants and their suggested nomenclature[J]. Pharmacogenet Genomics, 2009, 19(11):893-902.
[18] MOREB J S, BAKER H V, CHANG L J, et al. ALDH isozymes downregulation affects cell growth, cell motility and gene expression in lung cancer cells[J]. Mol Cancer, 2008, 7:87.
[19] CALDERARO J, NAULT J C, BIOULAC-SAGE P, et al. ALDH3A1 is overexpressed in a subset of hepatocellular carcinoma characterised by activation of the Wnt/βcatenin pathway[J]. Virchows Arch, 2014, 464(1):53-60.
[20] SAIKI J P, CAO H B, VAN WASSENHOVE L D, et al. Aldehyde dehydrogenase 3A1 activation prevents radiation-induced xerostomia by protecting salivary stem cells from toxic aldehydes[J]. Proc Natl Acad Sci USA, 2018, 115(24):6279-6284.
[21] HUANG T H, LI K Y, CHOI W S. Lymph node ratio as prognostic variable in oral squamous cell carcinomas:systematic review and meta-analysis[J]. Oral Oncol, 2019, 89:133-143.
[22] ZHAO Y R, WANG J L, XU C, et al. HEG1 indicates poor prognosis and promotes hepatocellular carcinoma invasion, metastasis, and EMT by activating Wnt/β-catenin signaling[J]. Clin Sci, 2019, 133(14):1645-1662.
[23] KROEPIL F, FLUEGEN G, TOTIKOV Z, et al. Down-regulation of CDH1 is associated with expression of SNAI1 in colorectal adenomas[J]. PLoS One, 2012, 7(9):e46665.
[24] GARBERS C, APARICIO-SIEGMUND S, ROSE-JOHN S. The IL-6/gp130/STAT3 signaling axis:recent advances towards specific inhibition[J]. Curr Opin Immunol, 2015, 34:75-82.
[25] HASHEMI V, MASJEDI A, HAZHIR-KARZAR B, et al. The role of DEAD-box RNA helicase p68(DDX5) in the development and treatment of breast cancer[J]. J Cell Physiol, 2019, 234(5):5478-5487.
[26] CHEN J, HUANG X P, LI N, et al. Narasin inhibits tumor metastasis and growth of ERα-positive breast cancer cells by inactivation of the TGF-β/SMAD3 and IL-6/STAT3 signaling pathways[J]. Mol Med Rep, 2020, 22(6):5113-5124.
[27] ATTIA Y M, TAWFIQ R A, ALI A A, et al. The FXR agonist, obeticholic acid, suppresses HCC proliferation & metastasis:role of IL-6/STAT3 signalling pathway[J]. Sci Rep, 2017, 7(1):12502.
[28] YANG Y H, WANG W, CHANG H, et al. Reciprocal regulation of miR-206 and IL-6/STAT3 pathway mediates IL6-induced gefitinib resistance in EGFR-mutant lung cancer cells[J]. J Cell Mol Med, 2019, 23(11):7331-7341.

ALDH3A1 activates GMA-induced malignant transformation of epithelial mesenchymal transition in 16HBE cells via the IL-6/STAT3 signalling pathway

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