A microRNA, miR-591, inhibits malignant pleural mesothelioma (MPM) cell proliferation and invasion, according to the study “Overexpression of micro ribonucleic acid-591 inhibits cell proliferation and invasion of malignant pleural mesothelioma cells,” published in the Thoracic Cancer journal.
MicroRNAs (miRNAs) are small non-coding RNA molecules shown to be involved in the initiation and progression of a number of cancers. They silence the expression of other genes by binding to their messenger RNA and leading to its degradation, exerting both beneficial or harmful functions in tumor progression depending on the genes they regulate.
To date, a limited number of studies have evaluated the differential expression of miRNAs in MPM samples. The research team, at the Tianjin Medical University in China, had previously identified a list of miRNAs that were altered in MPM tissues. One, miR-591, was shown to inhibit neuroblastoma cell growth and to decrease chemoresistance in ovarian cancer cells, but its role in MPM was unknown.
Investigators aimed at unraveling the role of miR-591 in the cellular biological effects of MPM. To do so, the team induced miR-591 overexpression in three different MPM cell lines, and addressed its effects on tumor cell growth, proliferation, invasion, and gene expression.
Results revealed that miR-591 was able to significantly inhibit MPM cell growth, proliferation, and invasion, suggesting that it may represent a novel therapeutic approach for MPM treatment.
To understand the mechanism through which miR-591 was acting on MPM cells, researchers analyzed the expression of genes associated with cell cycle homeostasis and apoptosis, and found that p21, a cell cycle regulator, and Bax, a pro-apoptotic gene, were both upregulated, which most likely induced cell arrest and apoptosis (programmed cell death).
In addition, metalloproteinase-2 (MMP2) and transforming growth factor (TGF)-β1, genes involved in invasion and metastasis, were found to be downregulated, accounting for the reduced mobility of the miR-591-overexpressing cells.
“[O]ur results show that overexpressing miR- 591 in vitro results in significantly decreased proliferation and invasion in MPM cell lines,” the authors concluded, adding, “Our study provides new insights into the molecular pathogenesis of MPM and suggests that miR-591 could be a potential therapeutic target for MPM.”
MPM is an aggressive cancer, often associated with asbestos exposure. It is resistant to available therapies, has a poor survival rate, and an urgent need to better understand the molecular mechanisms underlying MPM biology and develop new therapeutic approaches.