The group also examined cells lacking Dicer, and noted many similarities between Dicer-lacking and cyclin D1-lacking cells, in addition to failure of miRNA processing, suggesting a deeper connection between these two processes.
In addition to the in vitro studies, the researchers also examined over 2,200 patient samples. They found that patients with the luminal A subtype of breast cancer had increased levels of expression of both cyclin D1 and Dicer. Luminal A subtype of breast cancer is the most common type and also has the best prognosis. The more aggressive basal-like subtype of breast cancers, however, exhibited lower levels of cyclin D1 and Dicer, which would in turn globally reduce the level of mature miRNA. Indeed, lower levels of miRNAs have been observed in a number of human cancers.
"By linking the decrease in miRNA levels to Dicer, we show that a global decrease in miRNA processing may be important in the initiation and progression of certain cancers," says first author, Zuoren Yu, Ph.D., who holds a joint appointment at Jefferson's Kimmel Cancer Center and Tongji University School of Medicine in Shanghai, China.
Because the cyclin D1 gene has been implicated in a variety of other human cancers these findings may have broad implications for processing of non coding RNA in human tumorigenesis.
|Contact: Edyta Zielinska|
Thomas Jefferson University