Small RNA-Seq Transcriptome Profiling of Mesothelial and Mesothelioma Cell Lines Revealed microRNA Dysregulation after Exposure to Asbestos-like Fibers

Our plain-English summary of Small RNA-Seq Transcriptome Profiling of Mesothelial and Mesothelioma Cell Lines Revealed microRNA Dysregulation after Exposure to Asbestos-like Fibers, by V. Filetti, C. Lombardo, C. Loreto, et al (Biomedicines, 2023).

The study

• Authors: V. Filetti, C. Lombardo, C. Loreto, G. Dounias, M. Bracci, S. Matera, L. Rapisarda, V. Rapisarda, C. Ledda, E. Vitale
• Journal: Biomedicines
• Published: 2023;11(2)
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Environmental exposure to fibers of respirable size has been identified as a risk for public health. Experimental evidence has revealed that a variety of fibers, including fluoro-edenite, can develop chronic respiratory diseases and elicit carcinogenic effects in humans. Fluoro-edenite (FE) is a silicate mineral first found in Biancavilla (Sicily, Italy) in 1997. Environmental exposure to its fibers has been correlated with a cluster of malignant pleural mesotheliomas. This neoplasm represents a public health problem due to its long latency and to its aggression not alerted by specific symptoms. Having several biomarkers providing us with data on the health state of those exposed to FE fibers or allowing an early diagnosis on malignant pleural mesothelioma, still asymptomatic patients, would be a remarkable goal. To these purposes, we reported the miRNA transcriptome in human normal mesothelial cell line (MeT-5A) and in the human malignant mesothelioma cell line (JU77) exposed and not exposed to FE fibers. The results showed a difference in the number of deregulated miRNAs between tumor and nontumor samples both exposed and not exposed to FE fibers. As a matter of fact, the effect of exposure to FE fibers is more evident in the expression of miRNA in the tumor samples than in the nontumor samples. In the present paper, several pathways involved in the pathogenesis of malignant pleural mesothelioma have been analyzed. We especially noticed the involvement of pathways that have important functions in inflammatory processes, angiogenesis, apoptosis, and necrosis. Besides this amount of data, further studies will be designed for the selection of the most significant miRNAs to test and validate their diagnostic potential, alone or in combination with other protein biomarkers, in high-risk individuals' liquid biopsy to have a noninvasive tool of diagnosis for this neoplasm.

In plain English

This was a laboratory study of cells grown in dishes, not a study of people. The authors exposed two human cell lines, a normal mesothelial line (MeT-5A) and a malignant mesothelioma line (JU77), to fluoro-edenite fibers, an asbestos-like mineral from Biancavilla, Sicily. The doses were 10 and 50 µg/mL for 48 hours, and the exposed cells were compared with unexposed cells. The authors then used sequencing to measure microRNAs, which are small molecules that help control gene activity. The mesothelioma and normal cells differed in 333 microRNAs without fiber exposure, in 323 at 10 µg/mL and in 325 at 50 µg/mL. Within the normal cell line, fiber exposure changed 40 microRNAs at 10 µg/mL and 35 at 50 µg/mL. Within the mesothelioma line it changed 113 and 125. A computer analysis linked these changes to many biological pathways, including apoptosis (programmed cell death). The authors concluded that the fibers' effect on microRNAs was more evident in tumor cells than in normal cells. They said further studies are needed to select microRNAs and test them as possible diagnostic markers in high-risk individuals.

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: In vitro laboratory experiment on two human cell lines, using small RNA sequencing (microRNA profiling) and computer pathway analysis
• Who was studied: Two commercially obtained human cell lines: a normal mesothelial cell line (MeT-5A) and a malignant mesothelioma cell line (JU77). No human subjects were studied.
• Exposure: Fluoro-edenite (FE) fibers taken from the Biancavilla quarry (Sicily, Italy), added to the culture medium at final concentrations of 10 and 50 µg/mL for 48 hours. Unexposed cells served as controls.
• Main results:
  • In preliminary cell-viability tests, an exposure time of 48 hours was chosen because longer exposures did not cause statistically significant differences in cell viability.
  • Comparing mesothelioma (JU77) with normal (MeT5A) cells: 333 microRNAs differed without fiber exposure (145 up-regulated, 188 down-regulated), and 323 differed when both were exposed to 10 µg/mL (101 up-regulated, 222 down-regulated).
  • Comparing JU77 with MeT5A cells when both were exposed to 50 µg/mL fluoro-edenite: 325 microRNAs differed (124 up-regulated, 201 down-regulated).
  • In normal MeT5A cells, exposure versus no exposure changed 40 microRNAs at 10 µg/mL (22 up-regulated, 18 down-regulated) and 35 at 50 µg/mL (8 up-regulated, 27 down-regulated).
  • In mesothelioma JU77 cells, exposure versus no exposure changed 113 microRNAs at 10 µg/mL (24 up-regulated, 89 down-regulated) and 125 at 50 µg/mL (22 up-regulated, 103 down-regulated).
  • The normal (non-neoplastic) cell samples showed no microRNA changes in common between the two exposure doses.
  • Pathway analysis comparing JU77 with MeT5A cells involved 96 different pathways.
  • Of the pathways with negative scores in that comparison, 25 showed strong negative patterns, including apoptosis.
  • The authors stated that the effect of fiber exposure on microRNA expression was more evident in the tumor samples than in the nontumor samples.
• The authors' conclusion: The authors concluded that further studies are needed to select the most significant microRNAs and to test and validate their diagnostic potential, alone or with protein biomarkers, in high-risk individuals.

Topics

Medical terms in this study, explained in our Lexicon: Mesothelioma, Environmental Exposure, fluoro-edenite, Carcinogenic, Silicate, Biancavilla, Pleural Mesothelioma, Neoplasm.

Related studies

• Utilization of gene profiling and proteomics to determine mineral pathogenicity in a human mesothelial cell line (LP9/TERT-1) — J.M. Hillegass, A. Shukla, et al. (2010)
• Cytotoxicity, oxidative stress and genotoxicity induced by glass fibers on human alveolar epithelial cell line A549 — V. Rapisarda, C. Loreto, et al. (2015)
• Diagnostic and Prognostic Value of Three microRNAs in Environmental Asbestiform Fibers-Associated Malignant Mesothelioma — V. Filetti, C. Loreto, et al. (2021)
• Extensive temporal transcriptome and microRNA analyses identify molecular mechanisms underlying mitochondrial dysfunction induced by multi-walled carbon nanotubes in human lung cells — P. Nymark, P. Wijshoff, et al. (2015)
• Accelerated cell cycle progression of human regulatory T cell-like cell line caused by continuous exposure to asbestos fibers — S. Lee, H. Matsuzaki, et al. (2017)
• Aberrant expression of FoxP3 in a human T cell line possessing regulatory T cell‑like function and exposed continuously to asbestos fibers — M. Maeda, H. Matsuzaki, et al. (2018)

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