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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

Jiang, Zheshun LU orcid ; Person, Romane ; Lundh, Thomas LU ; Pineda, Daniela LU orcid ; Engfeldt, Malin LU ; Krais, Annette M LU orcid ; Hagberg, Jessika ; Ricklund, Niklas ; Vogel, Ulla and Saber, Anne T , et al. (2024) In Environment International 190. p.1-10
Abstract

BACKGROUND: 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.

OBJECTIVES: 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.

METHODS: 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... (More)

BACKGROUND: 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.

OBJECTIVES: 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.

METHODS: 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 (H19, MALAT1, NORAD), and four miRNAs (miR-142-3p, miR-15b-5p, miR-3940-5p, miR-451a).

RESULTS: Expression levels of lncRNAs MALAT1 and NORAD, and all four miRNAs, were significantly lower in Cr(VI) exposed workers compared with controls, and correlated significantly with RBC-Cr concentrations (rS = -0.16 to -0.38). H19 was non-significantly increased in exposed workers but significantly correlated with miR-142-3p (rS = -0.33) and miR-15b-5p (rS = -0.30), and NORAD was significantly positively correlated with all four miRNAs (rS = 0.17 to 0.46). In multivariate regression models adjusting for confounders, expressions of lncRNAs MALAT1 and NORAD and all miRNAs were still significantly lower in the exposed group compared with controls, and the expression decreased with increasing RBC-Cr concentrations.

CONCLUSIONS: 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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Environment International
volume
190
article number
108874
pages
1 - 10
publisher
Elsevier
external identifiers
  • pmid:38972113
ISSN
1873-6750
DOI
10.1016/j.envint.2024.108874
language
English
LU publication?
yes
additional info
Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.
id
076c1381-e3e1-4337-882e-9dfe86339ca8
date added to LUP
2024-07-08 10:10:46
date last changed
2024-07-11 02:19:10
@article{076c1381-e3e1-4337-882e-9dfe86339ca8,
  abstract     = {{<p>BACKGROUND: 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.</p><p>OBJECTIVES: 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.</p><p>METHODS: 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 (H19, MALAT1, NORAD), and four miRNAs (miR-142-3p, miR-15b-5p, miR-3940-5p, miR-451a).</p><p>RESULTS: Expression levels of lncRNAs MALAT1 and NORAD, and all four miRNAs, were significantly lower in Cr(VI) exposed workers compared with controls, and correlated significantly with RBC-Cr concentrations (rS = -0.16 to -0.38). H19 was non-significantly increased in exposed workers but significantly correlated with miR-142-3p (rS = -0.33) and miR-15b-5p (rS = -0.30), and NORAD was significantly positively correlated with all four miRNAs (rS = 0.17 to 0.46). In multivariate regression models adjusting for confounders, expressions of lncRNAs MALAT1 and NORAD and all miRNAs were still significantly lower in the exposed group compared with controls, and the expression decreased with increasing RBC-Cr concentrations.</p><p>CONCLUSIONS: 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.</p>}},
  author       = {{Jiang, Zheshun and Person, Romane and Lundh, Thomas and Pineda, Daniela and Engfeldt, Malin and Krais, Annette M and Hagberg, Jessika and Ricklund, Niklas and Vogel, Ulla and Saber, Anne T and Tondel, Martin and Albin, Maria and Broberg, Karin}},
  issn         = {{1873-6750}},
  language     = {{eng}},
  pages        = {{1--10}},
  publisher    = {{Elsevier}},
  series       = {{Environment International}},
  title        = {{Circulating lung-cancer-related non-coding RNAs are associated with occupational exposure to hexavalent chromium - A cross-sectional study within the SafeChrom project}},
  url          = {{http://dx.doi.org/10.1016/j.envint.2024.108874}},
  doi          = {{10.1016/j.envint.2024.108874}},
  volume       = {{190}},
  year         = {{2024}},
}