Circulating lung-cancer-related non-coding RNAs are associated with occupational exposure to hexavalent chromium – A cross-sectional study within the SafeChrom project,Environment International

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Circulating lung-cancer-related non-coding RNAs are associated with occupational exposure to hexavalent chromium – A cross-sectional study within the SafeChrom project
Environment International ( IF 10.3 ) Pub Date : 2024-07-03 , DOI: 10.1016/j.envint.2024.108874
Zheshun Jiang ₁ , Romane Person ₂ , Thomas Lundh ₁ , Daniela Pineda ₁ , Malin Engfeldt ₃ , Annette M Krais ₁ , Jessika Hagberg ₄ , Niklas Ricklund ₅ , Ulla Vogel ₆ , Anne T Saber ₆ , Martin Tondel ₇ , Maria Albin ₈ , Karin Broberg ₉ ,

Affiliation

Division of Occupational and Environmental Medicine, Department of Laboratory Medicine, Lund University, Lund, Sweden.
Division of Occupational and Environmental Medicine, Department of Laboratory Medicine, Lund University, Lund, Sweden; INSERM UMR-S 1124 and UMR-S 1139, Université Paris Cité, Paris, France.
Division of Occupational and Environmental Medicine, Department of Laboratory Medicine, Lund University, Lund, Sweden; Occupational and Environmental Medicine, Region Skåne, Lund, Sweden.
Department of Occupational and Environmental Health, Faculty of Business, Science and Engineering, Örebro University, Örebro, Sweden.
Department of Occupational and Environmental Health, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
National Research Centre for the Working Environment, Copenhagen, Denmark.
Occupational and Environmental Medicine, Department of Medical Sciences, Uppsala University, Uppsala, Sweden; Occupational and Environmental Medicine, Uppsala University Hospital, Uppsala, Sweden.
Division of Occupational and Environmental Medicine, Department of Laboratory Medicine, Lund University, Lund, Sweden; Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Division of Occupational and Environmental Medicine, Department of Laboratory Medicine, Lund University, Lund, Sweden; National Research Centre for the Working Environment, Copenhagen, Denmark; Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.

Hexavalent chromium (Cr(Ⅵ)) is classified as a group 1 human carcinogen and increases the risk of lung cancer. Non-coding RNAs (ncRNAs) have key regulatory roles in lung cancer, but less is known about their relation to Cr(Ⅵ) exposure. We aimed to 1) measure the expression of lung cancer-related circulating ncRNAs in exposed workers and controls; 2) assess associations between ncRNAs expression and Cr concentrations in red blood cells (RBC) and urine; and 3) evaluate correlations between the ncRNAs. The study included 111 Cr(VI) exposed workers and 72 controls recruited from the SafeChrom project. Cr concentrations were measured in RBC (biomarker of long-term exposure) and urine (biomarker of short-term exposure) samples. Long ncRNA (lncRNA) and microRNA (miRNA) were extracted from plasma followed by deoxyribonuclease treatment, complementary DNA synthesis, and quantitative real‐time polymerase chain reaction using target-specific assays for three lncRNAs (, , ), and four miRNAs (, , , ). Expression levels of lncRNAs and , and all four miRNAs, were significantly lower in Cr(VI) exposed workers compared with controls, and correlated significantly with RBC-Cr concentrations (r = −0.16 to −0.38). was non-significantly increased in exposed workers but significantly correlated with (r = −0.33) and (r = −0.30), and was significantly positively correlated with all four miRNAs (r = 0.17 to 0.46). In multivariate regression models adjusting for confounders, expressions of lncRNAs and and all miRNAs were still significantly lower in the exposed group compared with controls, and the expression decreased with increasing RBC-Cr concentrations. Cr(VI) exposure was inversely and in a dose–response manner associated with the expression of circulating non-coding RNA, which suggests ncRNAs as potential biomarkers for Cr(VI)-induced toxicity. Correlations between miRNAs and lncRNAs suggest that they participate in the same lncRNA-miRNA-messenger RNA regulatory axes, which may play important roles in Cr(VI) carcinogenesis.

中文翻译：

循环肺癌相关非编码 RNA 与职业接触六价铬有关——SafeChrom 项目内的一项横断面研究

六价铬 (Cr(Ⅵ)) 被列为第一类人类致癌物，会增加患肺癌的风险。非编码 RNA (ncRNA) 在肺癌中具有关键的调节作用，但人们对其与 Cr(Ⅵ) 暴露的关系知之甚少。我们的目的是 1) 测量暴露工人和对照中肺癌相关循环 ncRNA 的表达； 2) 评估 ncRNA 表达与红细胞 (RBC) 和尿液中 Cr 浓度之间的关联； 3) 评估 ncRNA 之间的相关性。该研究包括从 SafeChrom 项目招募的 111 名 Cr(VI) 暴露工人和 72 名对照组。测量红细胞（长期暴露的生物标志物）和尿液（短期暴露的生物标志物）样本中的 Cr 浓度。从血浆中提取长 ncRNA (lncRNA) 和 microRNA (miRNA)，然后进行脱氧核糖核酸酶处理、互补 DNA 合成和使用针对三种 lncRNA (, , ) 和四种 miRNA (, , , )。与对照组相比，Cr(VI) 暴露工人中 lncRNA 和以及所有四种 miRNA 的表达水平显着降低，并且与 RBC-Cr 浓度显着相关（r = -0.16 至 -0.38）。在暴露的工人中没有显着增加，但与 (r = -0.33) 和 (r = -0.30) 显着相关，并且与所有四种 miRNA 显着正相关 (r = 0.17 至 0.46)。在调整混杂因素的多变量回归模型中，与对照组相比，暴露组中lncRNA和所有miRNA的表达仍然显着较低，并且表达随着RBC-Cr浓度的增加而降低。 Cr(VI) 暴露与循环非编码 RNA 的表达成反比并以剂量反应方式相关，这表明 ncRNA 是 Cr(VI) 诱导毒性的潜在生物标志物。 miRNA 和 lncRNA 之间的相关性表明它们参与相同的 lncRNA-miRNA-信使 RNA 调节轴，这可能在 Cr(VI) 癌发生中发挥重要作用。

更新日期：2024-07-03

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