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

癌变·畸变·突变 ›› 2023, Vol. 35 ›› Issue (6): 405-411.doi: 10.3969/j.issn.1004-616x.2023.06.001

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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

王全凯^1,2, 金惠萍^1,2, 李昕苇^1,2, 崔旭芳^1,2, 顾轶婷¹, 乌瀚宝栎尔¹, 康同影¹, 许建宁^1,2

1. 中国疾病预防控制中心职业卫生与中毒控制所, 北京 100050;
2. 中国疾病预防控制中心创伤与化学中毒全国重点实验室, 北京 100050

收稿日期:2023-09-12 修回日期:2023-11-10 出版日期:2023-11-30 发布日期:2023-12-09
通讯作者: 许建宁
作者简介:王全凯，E-mail：kylewang@sina.com。
基金资助:
国家自然科学基金(81673221)

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

WANG Quankai^1,2, JIN Huiping^1,2, LI Xinwei^1,2, CUI Xufang^1,2, GU Yiting¹, WUHAN Baolier¹, KANG Tongying¹, XU Jianning^1,2

1. National Institute of Occupational Health and Poison Control, Chinese Center for Disease Control and Prevention, Beijing 100050;
2. State Key Laboratory of Trauma and Chemical Poisoning, Chinese Center for Disease Control and Prevention, Beijing 100050, China

Received:2023-09-12 Revised:2023-11-10 Online:2023-11-30 Published:2023-12-09

摘要/Abstract

摘要： 目的：甲基丙烯酸缩水甘油酯(GMA)作为一种广泛应用于各种复合材料合成和改性的化学物，已被国际癌症研究机构(IARC)归类为2A类致癌物，但其具体的致癌机制仍不明确。本研究拟探讨GMA诱导16HBE细胞发生恶性转化的关键分子机制是否与醛脱氢酶3A1(ALDH3A1)的表达变化相关。方法：在课题组前期建立的GMA诱导的恶性转化16HBE细胞模型中使用瞬时转染技术过表达ALDH3A1后，分别通过Western blot和qPCR法分析IL-6/磷酸化转录3激活剂(STAT3)通路及上皮间充质转化(EMT)过程标志物E钙黏蛋白(E-cadherin)、波形蛋白(Vimentin)、基质金属蛋白酶3(MMP3)、Snail的蛋白和mRNA表达情况。结果：Western blot和qPCR检测结果表明，与对照组相比，ALDH3A1过表达组细胞中E-cadherin表达增加，而IL-6、STAT3、p-STAT3、MMP3及Snail均表达降低(P<0.05)，同时MMP3、Snail、Vimentin转录水平下调(P<0.05)。ALDH3A1通过抑制IL-6/STAT3通路激活，减弱了GMA诱导的恶性转化16HBE细胞中EMT过程多个关键蛋白的表达。结论：ALDH3A1与GMA诱导的16HBE细胞恶性转化过程密切相关，并且通过IL-6/STAT3通路激活促使细胞上皮间充质转化能力增强。本研究的结果将有助于阐明GMA的致癌机制，并为GMA暴露的健康效应评估提供了潜在的生物标志物。

关键词: 甲基丙烯酸缩水甘油酯, 16HBE细胞, 醛脱氢酶3A1, EMT过程, IL-6/STAT3信号通路

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

中图分类号:

R730.2

王全凯, 金惠萍, 李昕苇, 崔旭芳, 顾轶婷, 乌瀚宝栎尔, 康同影, 许建宁. 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[J]. 癌变·畸变·突变, 2023, 35(6): 405-411.

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.

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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

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

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