环境与职业医学2025，Vol.42Issue(4)：475-481,7.DOI:10.11836/JEOM24393
circCCDC138在炭黑纳米粒子诱导人肺上皮细胞早期恶性转化中的作用
Role of circCCDC138 in early malignant transformation of human lung epithelial cells induced by carbon black nanoparticles
摘要
Abstract
[Background]With the large-scale production and application of carbon black nanoparticles(CBNPs),occupational and general exposure is obviously increasing.Related studies have shown that exposure to CBNPs can induce oxidative stress,inflammation,and DNA damage. [Objective]To establish a CBNPs-induced malignant transformation(C-BEAS-2B)model of human lung epithelial cells(BEAS-2B)and explore the role and mechanism of circCCDC138 in the malignant transformation process. [Methods]At 0,10,20,40 and 80 μg·mL-1 CBNPs concentrations,cell viability was detected by CCK8 assay.BEAS-2B cells were exposed to 20 mg·mL-1 CBNPs for three months,and a malignant transformation model of BEAS-2B induced by CBNPs was constructed.The migration and invasion abilities of the cells were detected by cell scratch and Transwell assays.The expressions of circ-CCDC138 in BEAS-2B and C-BEAS-2B were detected by qRT-PCR,and its stability was verified by a digestive resistance test.A cell model with interference or overexpression of circCCDC138 was constructed,and the expression of circCCDC138 in the cells was detected by quantitative reverse transcription-PCR.The cell cycle and apoptosis were determined by flow cytometry.Western blot was used to analyze the expression of p53 protein. [Results]The CBNPs used in the experiment were spherical particles with a chain-like structure.In the 20 μg·mL-1 CBNPs group,the re-duction in the viability of BEAS-2B cells was relatively small(10%).Compared with the control cells,the 20 μg·mL-1 CBNPs group showed more obvious cell migration and invasion at 24 h and 48 h,indicating that the exposure to CBNPs induced early malignant transformation of BEAS-2B cells(P<0.01).The circCCDC138 expression in C-BEAS-2B was upregulated in a time-dependent manner after exposure to CB-NPs.Compared with the C-BEAS-2B cells,the C-BEAS-2B cells over-expressing circCCDC138 exhibited arrested S phase progression(36.9%)and apoptosis resistance(P<0.01),along with down regulation of p53 protein expression in the cells(P<0.01),while the C-BEAS-2B cells interfering with circCCDC138 showed the opposite results(P<0.01). [Conclusion]BEAS-2B cells exposed to CBNPs(20 μg·mL-1)have significantly enhanced migration and invasion abilities,showing early malignant transformation characteristics.In addition,circCCDC138 is highly expressed in C-BEAS-2B cells with RNase R digestive resistance and increases in a time-dependent manner with CBNPs exposure.More importantly,circCCDC138 may promote the induction of malignant transformation of cells by inhibiting p53 protein expression.关键词
炭黑纳米粒子/BEAS-2B/circCCDC138/p53Key words
carbon black nanoparticle/BEAS-2B/circCCDC138/p53分类
医药卫生引用本文复制引用
李润锋,马丽纯,覃舒琳,刘雯..circCCDC138在炭黑纳米粒子诱导人肺上皮细胞早期恶性转化中的作用[J].环境与职业医学,2025,42(4):475-481,7.基金项目
国家自然科学基金项目(82204091) （82204091）
