Mesothelin, a gene that is highly expressed in mesothelioma and other cancers, is thought to have a driving role in this disease, regulating cancer cell proliferation and ability to invade other organs.
A microRNA, miR-21-5p, was now found to regulate the expression of the mesothelin gene, preventing the proliferation of tumor cells in malignant pleural mesothelioma (MPM). The finding could lead to new therapies aimed at controlling mesothelioma progression.
The study, “Identification Of MiR-21-5p As A Functional Regulator Of Mesothelin Expression Using MicroRNA Capture Affinity Coupled With Next Generation Sequencing,” was published in the journal PLoS One.
microRNAs are tiny RNA molecules that work by regulating protein production. They have the ability to bind to an mRNA molecule (a copy of the coding information required to produce a protein) and block the production of a given protein. Each microRNA can bind to many different mRNA molecules, which makes them powerful regulators of gene expression and protein production.
High levels of the mesothelin protein is found in MPM and some other cancers. Although this protein’s role is still elusive, it is believed that mesothelin works by regulating tumor proliferation and invasiveness.
Using a combination of laboratory techniques that allowed the isolation and identification of microRNAs bound to the mesothelin’s mRNA molecule, researchers identified 325 microRNAs that may be responsible for regulating mesothelin levels.
One of these was miR-21-5p, and researchers observed that higher levels of miR-21-5p led to lower mesothelin levels and lesser proliferation of cultured MPM cells. Likewise, blocking miR-21-5p increased mesothelin levels. Further experiments helped validate that this microRNA is a regulator of mesothelin levels in cultures of malignant and non-malignant cells.
“Although it has been extensively studied in cancer, miR-21-5p has been poorly investigated in MPM,” Chiara De Santi, with the Royal College of Surgeons in Ireland, and colleagues wrote. “Whether miR-21-5p expression is altered in other in vitro models of MPM or in the mesothelium of patients with MPM in vivo is unknown … The exact role of miR-21-5p in cancer development and progression is currently unclear and studies on pleural carcinogenesis are lacking.”
Although more studies are necessary to understanding how miR-21-5p is involved in MPM, researchers believe that it could play a protective role in this disease. miR-21-5p “appears to act as a tumor suppressor miRNA since it negatively regulated an oncogene,” they reported.