Dysregulation of microRNAs and tRNA-derived ncRNAs in mesothelial and mesothelioma cell lines after asbestiform fiber exposure

Our plain-English summary of Dysregulation of microRNAs and tRNA-derived ncRNAs in mesothelial and mesothelioma cell lines after asbestiform fiber exposure, by V. Filetti, A. La Ferlita, A. Di Maria, et al (Scientific Reports, 2022).

The study

• Authors: V. Filetti, A. La Ferlita, A. Di Maria, V. Cardile, A.C.E. Graziano, V. Rapisarda, C. Ledda, A. Pulvirenti, C. Loreto
• Journal: Scientific Reports
• Published: 2022;12(1):9181
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Experimental evidence demonstrated that fluoro-edenite (FE) can develop chronic respiratory diseases and elicit carcinogenic effects. Environmental exposure to FE fibers is correlated with malignant pleural mesothelioma (MPM). An early diagnosis of MPM, and a comprehensive health monitoring of the patients exposed to FE fibers are two clinical issues that may be solved by the identification of specific biomarkers. We reported the microRNA (miRNA) and transfer RNA-derived non coding RNA (tRNA-derived ncRNA) transcriptome in human normal mesothelial and malignant mesothelioma cell lines exposed or not exposed to several concentration FE fibers. Furthermore, an interactive mesothelioma-based network was derived by using NetME tool. In untreated condition, the expression of miRNAs and tRNA-derived ncRNAs in tumor cells was significantly different with respect to non-tumor samples. Moreover, interesting and significant changes were found after the exposure of both cells lines to FE fibers. The network-based pathway analysis showed several signaling and metabolic pathways potentially involved in the pathogenesis of MPM. From papers analyzed by NetME, it is clear that many miRNAs can positively or negatively influence various pathways involved in MPM. For the first time, the analysis of tRNA-derived ncRNAs molecules in the context of mesothelioma has been made by using in vitro systems. Further studies will be designed to test and validate their diagnostic potential in high-risk individuals' liquid biopsies.

© 2022. The Author(s).

In plain English

This was a laboratory study on two human cell lines, not on people. The authors grew a normal mesothelial cell line (MeT-5A) and a malignant mesothelioma cell line (JU77) and exposed them for 48 hours to fluoro-edenite, an asbestos-like amphibole fiber from Biancavilla, Sicily, at 10 and 50 µg/ml. They then sequenced two kinds of small RNA molecules: microRNAs and tRNA-derived non-coding RNAs. Without fiber exposure, 1171 of these molecules differed between the cancer cells and the normal cells. Within the normal cells, fiber exposure changed 7 molecules at 10 µg/ml and 64 at 50 µg/ml. Within the cancer cells, it changed 549 and 579. In viability tests, the normal cells were more sensitive to the fibers than the cancer cells. Comparing cancer with normal cells, a computer analysis of the changed microRNAs involved 39 pathways. The authors also built a literature network from 17,762 mesothelioma papers. The authors concluded that fiber effects on these molecules were more evident in the tumor cells. They called the work preliminary, with validation in an independent sample set still to come.

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: Laboratory (in vitro) experiment: small RNA sequencing of two human cell lines with and without fiber exposure, plus cell viability tests and a computer-built literature network
• Who was studied: Two human cell lines obtained from the American Type Culture Collection: MeT-5A (normal mesothelium) and JU77 (malignant mesothelioma). No human subjects.
• Exposure: Fluoro-edenite (FE) fibers, an amphibole from Biancavilla, Sicily, at 10 and 50 ug/ml for 48 hours for RNA sequencing; unexposed cells served as controls. Viability tests used 0.78 to 200 µg/ml from 6 to 72 hours.
• Main results:
  • Number of differentially expressed miRNAs and tRNA-derived ncRNAs between JU77 (cancer) and MeT-5A (normal) cells: 1171 when unexposed, 960 when both were exposed to 10 ug/ml FE fibers, and 969 when both were exposed to 50 ug/ml
  • In the normal MeT-5A cells, exposed versus unexposed: 7 molecules differentially expressed at 10 ug/ml and 64 at 50 ug/ml
  • In the JU77 mesothelioma cells, exposed versus unexposed: 549 molecules differentially expressed at 10 ug/ml and 579 at 50 ug/ml
  • In viability tests, MeT-5A (normal) cells were more sensitive to FE fibers than JU77 (cancer) cells
  • Neither cell line showed evident changes in shape after 48 hours of exposure, except cells in direct contact with the fibers, which took fibers inside them
  • Pathway analysis of the differentially expressed miRNAs, comparing JU77 with MeT-5A cells, showed negative and positive perturbation scores in 39 pathways
  • The literature-based mesothelioma network, built from 17,762 PubMed Central documents, contained 2,468,187 nodes and 8,508,601 edges
• The authors' conclusion: The authors concluded that the effect of FE fiber exposure on miRNA and tRNA-derived ncRNA expression was more evident in the tumor cells than in the non-tumor cells. They stated that further studies will select the most significant molecules to test and validate their diagnostic potential in high-risk individuals.
• Limitations the authors state:
  • The authors describe the work as preliminary. The most deregulated miRNAs still need validation by RT-qPCR in an independent sample set, and later in patients chronically exposed to FE.

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelioma, Asbestiform, fluoro-edenite, Carcinogenic, Environmental Exposure, Pleural Mesothelioma, Biomarker.

Related studies

• Small RNA-Seq Transcriptome Profiling of Mesothelial and Mesothelioma Cell Lines Revealed microRNA Dysregulation after Exposure to Asbestos-like Fibers — V. Filetti, C. Lombardo, et al. (2023)
• Role of the Ribonuclease ONCONASE in miRNA Biogenesis and tRNA Processing: Focus on Cancer and Viral Infections — M. Menegazzi, G. Gotte (2022)
• Diagnostic and Prognostic Value of Three microRNAs in Environmental Asbestiform Fibers-Associated Malignant Mesothelioma — V. Filetti, C. Loreto, et al. (2021)
• MicroRNAs dysregulation in human malignant pleural mesothelioma — V. Balatti, S. Maniero, et al. (2011)
• Overexpression of microRNA‑486 affects the proliferation and chemosensitivity of mesothelioma cell lines by targeting PIM1 — S. Pinelli, R. Alinovi, et al. (2021)
• A subset of microRNAs defining the side population of a human malignant mesothelioma cell line — M.C. Kim, N.Y. Kim, et al. (2017)

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