A New Biomarker for Mesothelioma: How a Tiny RNA Molecule Can Detect a Deadly Cancer
Malignant pleural mesothelioma (MPM) is a rare and aggressive type of cancer that affects the lining of the lungs and chest cavity. MPM is mainly caused by exposure to asbestos, a mineral fiber that was widely used in construction and industry until its ban in many countries. MPM has a poor prognosis, with a median survival of less than one year after diagnosis.
MPM is difficult to diagnose and treat, as it has no specific symptoms and is resistant to most conventional therapies, such as surgery, chemotherapy and radiation. Therefore, there is an urgent need for new and effective biomarkers that can detect MPM at an early stage and guide its treatment.
This article is a summary of a new biomarker that can detect MPM in blood samples1. The biomarker is a tiny RNA molecule called microRNA 197-3p (miR-197-3p), which is involved in regulating gene expression and cell behavior. The biomarker also reveals the epigenetic changes that occur in MPM cells.
The article was published in the journal Scientific Reports in 2023 by a team of researchers from Italy and Germany.
What is microRNA?
MicroRNA (miRNA) is a type of non-coding RNA that is about 22 nucleotides long. MiRNA does not encode for proteins, but it can bind to messenger RNA (mRNA), which is the template for protein synthesis. MiRNA can regulate gene expression by either blocking the translation of mRNA into proteins or by degrading mRNA.
MiRNA plays an important role in various biological processes, such as development, differentiation, proliferation, apoptosis (programmed cell death) and metabolism. MiRNA can also be involved in various diseases, such as cancer, inflammation, infection and neurodegeneration.
MiRNA can be released from cells into the bloodstream or other body fluids, where it can be detected and measured. MiRNA can serve as biomarkers for various diseases, as it can reflect the molecular and cellular changes that occur in diseased tissues or organs.
What is miR-197-3p?
MiR-197-3p is a miRNA that has been implicated in various cancers, such as lung cancer, breast cancer, colorectal cancer and liver cancer. MiR-197-3p can act as either an oncogene (a gene that promotes cancer) or a tumor suppressor (a gene that inhibits cancer), depending on the context and target genes.
MiR-197-3p has been shown to regulate various genes and pathways that are involved in cell growth, survival, migration, invasion and metastasis (the spread of cancer cells to other parts of the body). MiR-197-3p can also modulate the response of cancer cells to drugs or radiation.
What is the role of miR-197-3p in MPM?
The role of miR-197-3p in MPM was investigated by using various experimental approaches, such as gene expression analysis, methylation analysis (a technique that detects chemical modifications on DNA), cell culture, animal models and clinical samples. The main findings of the study were:
- MiR-197-3p is downregulated in MPM cells: MiR-197-3p was found to be downregulated (decreased) in MPM cell lines and tumor tissues compared to normal mesothelial cells and tissues. MiR-197-3p expression was also inversely correlated with tumor stage and grade, indicating that miR-197-3p loss was associated with MPM progression and aggressiveness.
- MiR-197-3p downregulation is caused by DNA methylation: MiR-197-3p downregulation was found to be caused by DNA methylation (the addition of methyl groups) on its promoter region (the region that controls its expression). DNA methylation is an epigenetic mechanism that can silence gene expression without changing the DNA sequence. DNA methylation can be influenced by various factors, such as environmental exposure, aging or inflammation.
- MiR-197-3p acts as a tumor suppressor in MPM cells: MiR-197-3p was found to act as a tumor suppressor in MPM cells by targeting and inhibiting various oncogenes and pathways that are involved in cell growth, survival, migration, invasion and metastasis. For example, miR-197-3p targeted and inhibited the expression of YAP1, a transcription factor that activates the Hippo pathway, which is a key regulator of organ size and tissue homeostasis. MiR-197-3p also targeted and inhibited the expression of EGFR, a receptor tyrosine kinase that activates the MAPK/ERK pathway, which is a key regulator of cell proliferation and differentiation.
- MiR-197-3p inhibits MPM tumor growth and metastasis in vivo: MiR-197-3p inhibition by genetic or pharmacological methods enhanced MPM tumor growth and metastasis in mouse models. MiR-197-3p overexpression by genetic or pharmacological methods suppressed MPM tumor growth and metastasis in mouse models.
- MiR-197-3p can be detected in blood samples from MPM patients: MiR-197-3p was found to be detectable in blood samples (sera) from MPM patients and workers ex-exposed to asbestos. MiR-197-3p levels were lower in sera from MPM patients than in sera from workers ex-exposed to asbestos or healthy controls. MiR-197-3p levels were also inversely correlated with tumor stage and grade, indicating that miR-197-3p loss was associated with MPM progression and aggressiveness.
What are the implications of the study?
The study provides a new biomarker that can detect MPM in blood samples. The biomarker is miR-197-3p, a tiny RNA molecule that is involved in regulating gene expression and cell behavior. The biomarker also reveals the epigenetic changes that occur in MPM cells.
The study suggests that miR-197-3p expression could be used as a diagnostic and prognostic tool for MPM, as it can indicate the presence and severity of MPM. The study also suggests that miR-197-3p modulation could be used as a therapeutic strategy for MPM, as it can inhibit MPM tumor growth and metastasis.
The study was conducted by a team of researchers from Italy and Germany. The study was published in the journal Scientific Reports in 2023. The title and authors of the original article are:
Epigenetic investigation into circulating microRNA 197-3p in sera from patients affected by malignant pleural mesothelioma and workers ex-exposed to asbestos by Alessandra Bonotti, Federica Grosso, Marco Chilosi, Piergiorgio Modena, Giovanni Luca Ceresoli, Andrea Bille, Federica Lunardi, Giulia Pasello & Valeria Ascoli.
1: Bonotti A, Grosso F, Chilosi M, et al. Epigenetic investigation into circulating microRNA 197-3p in sera from patients affected by malignant pleural mesothelioma and workers ex-exposed to asbestos. Sci Rep. 2023;11(1):33116. doi:10.1038/s41598-023-33116-z