A team of University of Florida Health Cancer Center researchers has discovered how modifications to a specific type of RNA play a crucial role in lung cancer. By modifying the RNA in laboratory cells, the researchers were able to inhibit the growth of lung cancer cells.
“Our finding suggests that erasing an abundant modification on certain types of RNA may be a promising way to therapeutically target lung cancer,” said Mingyi Xie, Ph.D., an associate professor in the department of biochemistry and molecular biology in the UF College of Medicine who led the study, published on Oct. 10 in Molecular Cell. “Our study establishes a new paradigm of RNA transcription in molecular biology, and the presence of high levels of this modification may be relevant in other cancers as well.”
Inside cells, RNA carries genetic information to make proteins. RNA can be dysregulated in dynamic and reversible processes, causing various diseases. One type of modification, called N6-mehtyladenosine, or m6A, plays a crucial role in RNA metabolism.
Research over the past decade has suggested that this modification affects how cancerous cells grow and how they respond to treatment. Studies have shown that abnormal m6A levels are involved in the progression of lung cancer, including cell proliferation, cancer spread and drug resistance. However, scientists do not fully understand how m6A contributes to cancer development.
In the new study, the UF researchers found that a particular type of abundant non-coding RNA, called 7SK small nuclear RNA, contained unusually high levels of m6A in lung cancer cells. 7SK plays an important role in RNA transcription, the process in which cells make new RNA.
“We found that removing these m6A caused lung cancer cells to encounter a problem in transcription, meaning they lose the ability to grow,” said Xie, who is a member of the UF Health Cancer Center’s Mechanisms of Oncogenesis research program. “This finding provides the molecular basis for potential therapeutics that modulate this type of RNA to treat lung cancer.”
The researchers studied the RNA behavior in non-small cell lung cancer cells, the most common type of lung cancer. Further studies are needed to pinpoint the specific m6A sites that contribute to transcription regulation, the researchers said.
The study was funded in part from the National Institutes of Health, the American Cancer Society and the Florida Department of Health Live Like Bella Childhood Cancer Foundation.
Co-authors include lead author Yuzhi Wang, Ph.D., a postdoctoral associate in Xie’s lab; Jiang Bian, Ph.D., director of the Cancer Informatics Shared Resource at the UF Health Cancer Center who serves as chief scientist and chief research information officer at UF Health; and Maurice Swanson, Ph.D., a professor in the department of molecular genetics and microbiology in the UF College of Medicine.
Research at the UF Health Cancer Center receives crucial support from the Casey DeSantis Cancer Research Act (Fla. Stat. § 381.915).