MicroRNA Molecule Found to Be a Potent Tumor Suppressor in Lung Cancer
New research shows that microRNA-486 (miR-486) is a potent tumor-suppressor molecule in lung cancer, and that it helps regulate the proliferation and migration of lung cancer cells, as well as the induction of apoptosis in those cells. Published in the Proceedings of the National Academy of Sciences, the study suggests that miR-486 may serve as a biomarker for patients with lung cancer who might respond to treatment with insulin growth factor inhibitors.
Study Details
The preclinical study was led by researchers at the Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James). The researchers examined lung tumor samples from 81 patients with stage I non–small cell lung cancer and tumor cell lines. Analyses identified miR-486 as the most decreased of microRNAs in the cells, so the researchers chose it for further investigation.
The study found that miR-486 directly targets the insulin growth factor pathway, which is important for cell survival and proliferation. Alternations in the pathway are believed to play an early role in tumor initiation and progression.
Link Between miR-486 and p53
The researchers further found that miR-486 is itself regulated by the tumor-suppressor gene p53, the most frequently altered gene in human cancers, and that activity of miR-486 is partially dependent upon functional p53.
“It wasn’t known whether miR-486 functioned as an oncogene or a tumor-suppressor gene in lung cancer,” said cocorresponding author Patrick Nana-Sinkam, MD, Associate Professor of Medicine and a researcher with the OSUCCC – James Molecular Biology and Cancer Genetics Program.
“miR-486 appears to be a biomarker for lung cancer, but its mechanisms of action remain unclear," he said. "These findings show that miR-486 serves a tumor-suppressor function in lung cancer, and that miR-486 action is partially dependent on p53.”
“This partial reliance of one tumor suppressor on another was a surprise,” said principal investigator and cocorresponding author Carlo M. Croce, MD, Director of Ohio State’s Human Cancer Genetics program and the John W. Wolfe Chair in Human Cancer Genetics at the OSUCCC – James. “We don’t know yet what implications, if any, this might have for the development of targeted therapies.”
Funding from the NIH/National Cancer Institute supported this research.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
