Genome-wide profiling reveals novel microRNAs in hand-spinning-specific chrysotile exposure

Our plain-English summary of Genome-wide profiling reveals novel microRNAs in hand-spinning-specific chrysotile exposure, by J. Jia, X. Guo, L. Feng, et al (Epigenomics, 2019).

The study

• Authors: J. Jia, X. Guo, L. Feng, X. Yin, L. Zhu, J. Li, D. Yu, Y. Fang, Z. Jiang, M. Yu, H. Xia, L. Shi, L. Ju, M. Zhang, Y. Xiao, C.A. Lu, W. Shi, X. Zhang, J. Lou
• Journal: Epigenomics
• Published: 2019;11(5):511-525
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Aim: We aimed to explore miRNA expression profiles in hand-spinning chrysotile exposed workers and their potential influencing factors.

Methods: miRNA array technique was applied to screen differentially expressed miRNAs between plasma samples from three exposed workers and three controls. Then, seven selected miRNAs were validated in 143 workers and 100 controls, and the potential influencing factors were revealed by multiple linear regression. Finally, the expression levels of those seven miRNAs were evaluated in human mesothelial cells (Met-5A) that were exposed to chrysotile at 5 μg·cm-2 for 8, 24 and 48 h, respectively.

Results & Conclusion: Hand-spinning chrysotile exposure can result in differential expression of miRNAs. Several of those miRNAs have positive correlations with asbestos exposure.

In plain English

This cross-sectional study from China measured microRNAs (short RNA molecules that help regulate genes), using blood plasma, in people with a history of hand-spinning chrysotile asbestos work. Subjects came from a county in southeastern China where asbestos products had been made since the 1950s. There were 143 occupationally exposed people with normal chest x-rays (87% women) and 100 unexposed controls. A microarray first compared plasma from three exposed people and three controls and found 40 microRNAs that differed. Fifteen of these were then checked with a second laboratory method in the larger group. Six were lower in the exposed group, matching the array. Within the exposed group, five of these were positively correlated with estimated exposure level. In laboratory human mesothelial cells exposed to chrysotile, all but one of the six were lower at 8 hours and then began to rise. The authors concluded that hand-spinning chrysotile exposure can result in differential expression of microRNAs. They noted several limits: the cross-sectional design, other exposures, genetic variation, a small screening sample, and the unequal share of women between groups may have affected the results.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Cross-sectional study in people: a microRNA array screening of 3 exposed workers and 3 controls, followed by qRT-PCR validation in the larger group. It was combined with a laboratory experiment on a human mesothelial cell line (Met-5A).
• Who was studied: 243 subjects from a county in southeastern China with asbestos-product manufacturing since the 1950s. The asbestos-exposed group was 143 occupationally exposed people whose chest x-rays showed no changes (124 women, 19 men). The control group was 100 healthy people not exposed to any asbestos, with normal chest x-rays (45 women, 55 men). Median age was 69 in both groups.
• Exposure: Occupational hand-spinning chrysotile asbestos exposure. Median total dust concentration was 0.7 mg/m3 in household textile workshops and 5.9 mg/m3 in the textile manufactory. In the exposed group, median occupational exposure duration was 13 years (interquartile range 11 to 17). Median estimated potential exposure level was 62 mg/m3 × years (interquartile range 10 to 94). In the cell experiment, Met-5A cells were exposed to chrysotile at 5 micrograms per square centimetre for 8, 24 and 48 hours, with phosphate-buffered saline as control.
• Main results:
  • In the array comparison of 3 exposed workers and 3 controls, 40 microRNAs differed significantly: 19 were higher and 21 were lower in the exposed group.
  • Fifteen of the microRNAs found by the array were selected for validation by qRT-PCR in a larger number of people.
  • In the qRT-PCR validation, seven were lower in the exposed group than in controls: hsa-miR-3960, hsa-miR-4497, hsa-miR-4508, hsa-miR-6089, hsa-miR-6125, hsa-miR-6775-5p and hsa-miR-6865-5p. The result for hsa-miR-6865-5p did not agree with the array, leaving six validated microRNAs.
  • In the exposed group, levels of hsa-miR-3960, hsa-miR-4497, hsa-miR-6089 and hsa-miR-6125 were positively correlated with exposure duration. The Spearman coefficients were 0.19 (p = 0.03), 0.29 (p less than 0.01), 0.27 (p less than 0.01) and 0.56 (p less than 0.001).
  • In the exposed group, hsa-miR-3960, hsa-miR-4497, hsa-miR-4508, hsa-miR-6089 and hsa-miR-6125 were positively correlated with potential exposure level. The figures show R values of 0.2487, 0.2801, 0.2377, 0.2301 and 0.2915. The same five were negatively correlated with age at first exposure.
  • In multiple linear regression in the exposed group, potential exposure level was significantly associated with expression of hsa-miR-3960 (b = 0.00423; p = 0.0105), hsa-miR-4497 (b = 0.00398; p = 0.0028), hsa-miR-4508 (b = 0.00453; p = 0.0134), hsa-miR-6089 (b = 0.00221; p = 0.0163) and hsa-miR-6125 (b = 0.00344; p = 0.0018).
  • For hsa-miR-6775-5p, neither environmental exposure (b = 0.41119; p = 0.0948) nor family exposure (b = -0.39783; p = 0.1057) had an effect on expression.
  • In chrysotile-treated Met-5A mesothelial cells, all of the six validated microRNAs except hsa-miR-4508 were lower than in control cells at 8 hours and then began to rise. hsa-miR-3960 returned to normal by 48 hours.
  • Computer prediction software identified 227 possible target genes for the six validated microRNAs. Some of these genes were associated with the TGF-β and PI3K-AKT signaling pathways.
• The authors' conclusion: The authors concluded that hand-spinning chrysotile exposure can result in differential expression of microRNAs. They concluded that several of these microRNAs had positive correlations with asbestos exposure and may play a role in the TGF-β and PI3K-Akt signaling pathways.
• Limitations the authors state:
  • Subjects were exposed to various other chemicals and non-chemical stressors that may affect microRNA expression. The findings may be related to other exposures.
  • The screening (array) part of the study used a small sample.
  • The proportion of women differed between the control and exposed groups, which may have influenced the results.
  • The influence of genetic variation on microRNA expression could not be excluded.
  • The cross-sectional design limits whether past asbestos exposure can be held responsible for the microRNA changes. The authors called for prospective cohort studies.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Chrysotile.

Medical terms in this study, explained in our Lexicon: Chrysotile, Mesothelial Cells, Asbestos Exposure.

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