Tiny molecules could hold enormous implications for cancer diagnosis and treatment. A discovery by University of Maryland School of Dentistry (UMSOD) researchers reveals new information about the important role pi-RNA molecules play in cellular function, and how those molecules are impacted by cancer.
In a paper published in Nature Communications, Li Mao, MD, chairman of the Department of Oncology & Diagnostic Sciences, and collaborators set out to describe how pi-RNA molecules function in adult cells. RNA (ribonucleic acid), present in all living cells, carries genetic information from DNA to proteins. Pi-RNAs are a recently discovered subset of non-coding RNA, or ncRNA, which cannot be converted into proteins. For years, researchers have known that these short, pi-RNAs play an important role in embryonic cells during human development, but little information existed about the role of pi-RNA in adult cells.
Mao and his collaborators examined healthy adult lung cells and lung cancer cells to see whether pi-RNA exist and how they function in each condition. At the outset of the study, the researchers encountered their first surprising result. Using special technology known as RNA sequencing, they identified 555 pi-RNAs in these lung cells, a much larger number than anticipated, including 295 pi-RNAs that do not currently exist in databases. They also discovered that many of those pi-RNAs presented at different levels, depending on whether the cell was healthy or cancerous. “Our research suggests that, not only do these pi-RNA express in adult cells, they may also be functionally important,” Mao says. “These molecules change with different disease statuses, so there is a suggestion that they play a role in the disease processes.”
To drill deeper into this discovery, the researchers closely examined one particular pi-RNA, number 163. In cancerous cells, this molecule was expressed at an extremely low level, leading researchers to believe that it had a functional role for the disease. “What surprised us is that pi-RNA 163 turns out to be a molecule that regulates protein function. This is a mechanism that no one expected for this type of molecule,” Mao says. “This discovery is totally out of the blue in terms of traditional functionality for pi-RNAs or any short ncRNA.”
The researchers found that, due to its function in regulating proteins called ERM (ezrin, radixin and moesin), the tiny pi-RNA 163 may play a role in cancer invasion and metastasis. When pi-RNA 163 is unable to function at its normal level, the proteins it regulates are also unable to operate normally. That irregular protein function likely contributes to the intensity and spread of cancer cells. The discovery holds huge implications for future cancer detection and treatment, Mao says. “Once we understand how these pi-RNAs and the proteins interact, we can block that interaction or we can enhance it, which could impact the cancer cells,” says Mao. “If the phenomenon we identified is a general physiology of human cells, the discovery may have a greater impact because pi-RNAs may also play an important role in diseases beyond cancer.”
While the research is still in its preliminary phases, Mao is confident this discovery holds a key for future treatments. “From a cancer patient’s point of view, this discovery could be another hope; a hope for the future to improve medicine,” says Mao. “This research could reveal a way to prevent and treat cancer and other diseases.”
The University of Maryland, Baltimore has filed a patent application for the discovery and is seeking partners to further develop the technology toward clinical applications. To learn more about partnering with the University of Maryland for technology development, visit http://umventures.org.