MicroRNA molecule found to be a potent tumor-suppressor in lung cancer

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). It found that microRNA-486 (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.

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.

Published in the Proceedings of the National Academy of Sciences, the study suggests that miR-486 might serve as a biomarker for lung-cancer patients who might respond to treatment with insulin-growth-factor inhibitors.

"It wasn't known whether miR-486 functioned as an oncogene or a tumor-suppressor gene in lung cancer," says co-corresponding 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 says. "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," says principal investigator and co-corresponding 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."

MicroRNAs are a class of short, non-coding RNAs that regulate the translation or degradation of messenger RNA and therefore the proteins that cells make. Research is showing that certain microRNAs are frequently dysregulated in cancer.

Nana-Sinkam and his colleagues examined lung-tumor samples from 81 patients with stage-1 nonsmall-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.

INFORMATION:

Funding from the NIH/National Cancer Institute (grant CA152758) supported this research.

Other researchers involved in this study were Yong Peng, Yuntao Dai, Charles Hitchcock, Xiaojuan Yang, Edmund S. Kassis, Zhenghua Luo, Hui-Lung Sun, Ri Cui, Huijun Wei, Taewan Kim, Tae Jin Lee, Young-Jun Jeon, Gerard J. Nuovo, Stefano Volinia, Jianhua Yu and Carlo M. Croce of The Ohio State University; Lunxu Liu of Sichuan University, China; and Qianchuan He of Fred Hutchinson Cancer Research Center.

The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute strives to create a cancer-free world by integrating scientific research with excellence in education and patient-centered care, a strategy that leads to better methods of prevention, detection and treatment. Ohio State is one of only 41 National Cancer Institute (NCI)-designated Comprehensive Cancer Centers and one of only four centers funded by the NCI to conduct both phase I and phase II clinical trials. The NCI recently rated Ohio State's cancer program as "exceptional," the highest rating given by NCI survey teams. As the cancer program's 228-bed adult patient-care component, The James is a "Top Hospital" as named by the Leapfrog Group and one of the top cancer hospitals in the nation as ranked by U.S.News & World Report.

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