The role of non-coding RNAs in pleural mesothelioma

Our plain-English summary of The role of non-coding RNAs in pleural mesothelioma, by G. Tonnini, G. Di Mauro, M.L. Tramarin, et al (Translational Oncology, 2025).

The study

• Authors: G. Tonnini, G. Di Mauro, M.L. Tramarin, A. Meneghetti, I. Bononi, C. Mazziotta, J.C. Rotondo, E. Mazzoni, M.R. Iaquinta, E. Trabetti, C. Bombieri, M. De Mattei, M. Tognon, F. Martini
• Journal: Translational Oncology
• Published: 2025;62:102547
• Type of article: Review
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Pleural mesothelioma (PM) is a rare and highly aggressive tumor, primarily caused by asbestos exposure. Its long latency period and late-stage diagnosis severely limit therapeutic options.

Aim: Recent evidence suggests that non-coding RNAs (ncRNAs)-including microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs)-play key roles in PM biology. This review aims to synthesize current knowledge on ncRNA dysregulation in PM and explore their diagnostic, prognostic, and therapeutic potential.

Scope: We summarize studies addressing the expression and function of ncRNAs in tumors and in circulating biofluids of PM patients. Particular attention is given to how ncRNAs regulate proliferation, apoptosis, and migration, and how competing endogenous RNA (ceRNA) networks shape gene regulation in PM.

Novelty And Conclusion: Unlike previous reviews, this work integrates findings across different classes of ncRNAs and their interactions, highlighting the emerging concept of ceRNA networks in PM. By bridging molecular mechanisms with potential clinical applications, we provide an updated and comprehensive framework that may inform future strategies for diagnosis, prognosis, and targeted therapy in PM.

Copyright © 2025. Published by Elsevier Inc.

In plain English

This article was a review. It did not report new research. It summarized earlier studies of non-coding RNAs in pleural mesothelioma. Non-coding RNAs are RNA molecules that do not make proteins but help control genes, and the review covered three kinds: microRNAs, long non-coding RNAs and circular RNAs, measured in tumor tissue, cancer cells and blood. The authors noted that the disease is associated with asbestos fiber exposure in 70–80% of cases. In the studies reviewed, an early study found 23 microRNAs that differed between mesothelioma tissue and normal pleura, and asbestos was reported to alter microRNA patterns. A blood microRNA, miR-126, was first proposed as a marker, but later studies found it could not tell mesothelioma patients apart from asbestos-exposed people. Only one circular RNA, circPLK1, had so far been linked to the disease. An early-stage trial of a microRNA-based treatment showed limited clinical results and some signs of toxicity. The authors concluded that this research is promising for finding markers and therapies. They cautioned that some findings had not been independently validated or were conflicting.

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: Narrative review of published studies on non-coding RNAs (microRNAs, long non-coding RNAs, circular RNAs) in pleural mesothelioma; no new data were collected
• Who was studied: No study population of its own; the review covered published studies of pleural mesothelioma cancer cells, tumor tissue and blood samples
• Exposure: Not an exposure study. The authors describe pleural mesothelioma as associated with asbestos fiber exposure in 70–80% of cases. Some of the reviewed studies looked at how asbestos alters microRNA patterns. No specific fiber types or doses are analysed.
• Main results:
  • In the reviewed literature, the first study of microRNAs in pleural mesothelioma tissue (Guled et al.) found 23 microRNAs expressed differently from normal pleura
  • The reviewed studies reported that asbestos alters microRNA expression patterns
  • A cited study reported that pleural mesothelioma tissue showed significantly higher levels of miR-125a-5p and miR-484 than benign asbestos-related pleural effusions
  • Circulating miR-126 was first proposed as a blood marker, but later studies found it could not distinguish pleural mesothelioma patients from asbestos-exposed individuals
  • A cited study reported overall sensitivity and specificity of around 70% for circulating miR-126, which the authors called satisfactory but not optimal
  • Cited studies reported that miR-197-3p was lower in asbestos-exposed subjects but detectable in pleural mesothelioma patients
  • A cited study (Ferrari et al.) reported that combining blood miR-103a-3p and miR-30e-3p with the protein markers Fibulin-3, HMGB1 and mesothelin improved diagnostic accuracy
  • Among long non-coding RNAs, cited work reported that GAS5 acts as a tumor suppressor and is reduced in pleural mesothelioma cells
  • circPLK1 is the only circular RNA so far found to be implicated in pleural mesothelioma
  • A cited phase 1 study of a miR-16 mimic treatment (TargomiRs), given to pleural mesothelioma patients whose earlier chemotherapy had failed, showed limited clinical results and some signs of toxicity
• The authors' conclusion: The authors concluded that research on non-coding RNAs is promising for finding early prognostic markers and therapies for pleural mesothelioma, but that much remains to be done before patients could benefit clinically
• Limitations the authors state:
  • Some claims in the review may have limited strength, because findings may not have been independently validated and some data conflict
  • Because pleural mesothelioma is rare, there are fewer studies than for more common cancers
  • Studies of circulating microRNAs as markers differ in how they chose control groups and normalized data, and their sample sizes may not always be sufficient
  • The authors stated that much remains to be done to show how patients might benefit clinically from these non-coding RNAs

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Asbestos Exposure, Latency, Apoptosis, Prognosis, Targeted Therapy.

Related studies

• Long non coding RNAs (lncRNAs) are dysregulated in Malignant Pleural Mesothelioma (MPM) — C.M. Wright, M.B. Kirschner, et al. (2013)
• Relations between approved platinum drugs and non-coding RNAs in mesothelioma — B. Biersack (2018)
• Interplay of non-coding RNAs and approved antimetabolites such as gemcitabine and pemetrexed in mesothelioma — B. Biersack (2018)
• Epigenetic investigation into circulating microRNA 197-3p in sera from patients affected by malignant pleural mesothelioma and workers ex-exposed to asbestos — G. Di Mauro, F. Frontini, et al. (2023)
• Sera from Patients with Malignant Pleural Mesothelioma Tested Positive for IgG Antibodies against SV40 Large T Antigen: The Viral Oncoprotein — E. Mazzoni, I. Bononi, et al. (2022)
• Proliferation of pleural mesothelioma cells is enhanced by the microRNA-197-3p activity — I. Bononi, G. Di Mauro, et al. (2026)

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