Microbiomes, Epigenomics, Immune Response, and Splicing Signatures Interplay: Potential Use of Combination of Regulatory Pathways as Targets for Malignant Mesothelioma

Our plain-English summary of Microbiomes, Epigenomics, Immune Response, and Splicing Signatures Interplay: Potential Use of Combination of Regulatory Pathways as Targets for Malignant Mesothelioma, by B.P. Setlai, Z.L. Mkhize-Kwitshana, R. Mehrotra, et al (International Journal of Molecular Sciences, 2022).

The study

• Authors: B.P. Setlai, Z.L. Mkhize-Kwitshana, R. Mehrotra, T.V. Mulaudzi, Z. Dlamini
• Journal: International Journal of Molecular Sciences
• Published: 2022;23(16)
• Type of article: Review
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant mesotheliomas (MM) are hard to treat malignancies with poor prognosis and high mortality rates. This cancer is highly misdiagnosed in Sub-Saharan African countries. According to literature, the incidence of MM is likely to increase particularly in low-middle-income countries (LMICs). The burden of asbestos-induced diseases was estimated to be about 231,000 per annum. Lack of awareness and implementation of regulatory frameworks to control exposure to asbestos fibers contributes to the expected increase. Exposure to asbestos fibers can lead to cancer initiation by several mechanisms. Asbestos-induced epigenetic modifications of gene expression machinery and non-coding RNAs promote cancer initiation and progression. Furthermore, microbiome-epigenetic interactions control the innate and adaptive immunity causing exacerbation of cancer progression and therapeutic resistance. This review discusses epigenetic mechanisms with more focus on miRNAs and their interaction with the microbiome. The potential use of epigenetic alterations and microbiota as specific biomarkers to aid in the early detection and/or development of therapeutic targets is explored. The advancement of combinatorial therapies to prolong overall patient survival or possible eradication of MM especially if it is detected early is discussed.

In plain English

This article was a narrative review, not a new study, and it did not describe how the literature was chosen. It discussed how asbestos fibers may lead to malignant mesothelioma through changes in gene regulation (epigenetics). It focused on small regulatory molecules called microRNAs and how they may interact with the microbiome (microbes living in the body), the immune system, and RNA splicing. It did not name specific asbestos fiber types. Among the published work it described, one study found that 54 of 80 high-income countries, but only 11 of 78 low-middle-income countries, reported mesothelioma deaths to WHO. A South African study collected 1581 bulk samples from structures in three provinces, not all of which were demolished, and found asbestos in 54.8% of them. Other cited studies reported that a microRNA, miR-197-3p, was significantly lower in people with work-related asbestos exposure than in controls, and that 36 microbial species were found in mesothelioma tissue. The authors called for asbestos awareness campaigns. They concluded that combined epigenetic, microbial and immune pathways could be manipulated to improve treatment, presenting this as a possibility.

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 literature (no search methods described)
• Who was studied: No study population of its own. The review covered published studies of malignant mesothelioma, including human tissue, serum, cell lines and animal models, with a table of microRNA findings from 2017 to 2022.
• Exposure: Asbestos fibers in general (no specific fiber types named), including asbestos products and asbestos cement roofing in Sub-Saharan Africa.
• Main results:
  • Cited study (Chimed-Ochir et al.): 54 (68%) of 80 high-income countries reported mesothelioma deaths to WHO, compared with 11 (14%) of 78 low-middle-income countries.
  • Cited South African NIOH study of structures in Gauteng, Mpumalanga and the Western Cape, not all of which were demolished: 54.8% of the 1581 bulk samples contained asbestos. Asbestos was found in 16.1% (227) of air filters after demolition.
  • Cited study: miR-197-3p was significantly lower in individuals with work-related asbestos exposure than in controls, and was suggested as a possible biomarker of asbestos exposure.
  • Cited study: deregulated methylation of miR-34b/c was seen in 85% of malignant pleural mesothelioma tumors.
  • Cited study (Higuchi et al.): 36 microbial species were identified in mesothelioma tissues, with Streptococcus australis and Ralstonia pickettii the most abundant.
  • Cited study: in diffuse malignant peritoneal mesothelioma, high SF3B1 levels correlated significantly with shorter overall and progression-free survival.
• The authors' conclusion: The authors called for awareness campaigns about asbestos dangers, especially in communities still using asbestos products. They concluded that the combined epigenetic microRNA, microbiota and immune systems could be manipulated to enhance immunotherapy response or to develop treatments for malignant mesothelioma.

Topics

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

Medical terms in this study, explained in our Lexicon: Malignant Mesothelioma, Prognosis, Biomarker.

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