A molecule has been discovered that could lead to noninvasive detection and treatment of lung cancer. RNA sequencing was used to examine airway epithelial cells and to identify a regulatory molecule that is less abundant in people with lung cancer. This molecule inhibits lung cancer cell growth, and it may aid in diagnosing lung cancer in earlier stages and in treating the disease.
According to the National Cancer Institute (NCI), lung cancer is the leading cause of cancer death among both men and women in the United States, and 90% of lung cancer deaths among men and approximately 80% of lung cancer deaths among women are due to smoking. The NCI also estimates that approximately 373,489 Americans are living with lung cancer and its treatment costs approximately $10.3 billion in the United States each year.
MicroRNAs are a new class of molecules classified as important regulators of the activity of other genes. In this study, the research team used a next-generation RNA sequencing technology to identify a microRNA, miR-4423. MiR-4423 was found in epithelial airway cells, and it plays a major role in how these cells develop. In epithelial cells from the airways of smokers with lung cancer, levels of miR-4423 were decreased.
“These results suggest measuring the levels of microRNAs like miR-4423 in cells that line the airway could aid in lung cancer detection through a relatively non-invasive procedure,” said senior author Avrum Spira, MD, MSc, of Boston University School of Medicine (BUSM) in Massachusetts. This study was published in the Proceedings of the National Academy of Sciences (2103; doi:10.1073/pnas.1220319110).
Using experimental models in vitro and in vivo, the research team demonstrated that miR-4423 can both promote the development of the normal airway cells and suppress lung cancer cell growth. This suggests that miR-4423 plays a major regulatory role in cell fate decisions made by airway epithelial cells during maturation and low levels of miR-4423 contributes to lung cancer development. Interestingly, throughout the body, miR-4423 seems only to be present in high levels in the airway epithelium, suggesting this could be a very specific process occurring only in the lungs.
“Our findings open up the option to study whether returning miR-4423 levels to normal in the airway could help stop cancer growth and potentially be a way to treat lung cancer,” said lead author Catalina Perdomo, PhD, a researcher in the division of computational biomedicine at BUSM.
“Interestingly, when we examined the genomes of other species for microRNAs that might function like miR-4423, we did not find anything in nonprimates,” said Marc Lenburg, PhD, an associate professor in computational medicine and bioinformatics at BUSM who is one the study’s senior authors. “It makes us wonder what it is different about lung development in primates and excited that this could be a very specific process to target for lung cancer treatment.”