Recent findings at the University of Pittsburgh School of Medicine are unraveling how RNA molecules influence prostate cancer progression. Bino John, PhD, an adjunct professor at Pittsburgh School of Medicine, led his research team in the discovery of two new classes of RNA that closely associate with human Y-box binding protein 1 (YB-1), which has been shown to correlate to poor patient outcomes in prostate cancer. The team’s results are published in RNA, a scientific journal from the RNA Society.
“Many small RNAs known as microRNAs already have been shown to correlate with different grades of prostate cancer and could potentially serve as biomarkers for diagnosis and treatment,” said Dr. John, in a news release from the university. “We did this study after computer models led us to hypothesize that there was a connection between YB-1 and microRNAs. What started out as a curiosity-driven experiment ended up being an exhilarating treasure hunt over four years, culminating in the discovery of two big molecular finds from human cells.”
These two big finds are called YB-1 associated short non-coding RNAs (shyRNAs) and YB-1 associated small RNAs (smyRNAs). smyRNAs are smaller versions of shyRNAs that have undergone processing within the cell. Dr. John and the rest of his team at Pittsburgh School of Medicine published these findings in the article, “Noncoding RNAs That Associate With YB-1 Alter Proliferation in Prostate Cancer Cells.”
Identifying RNAs that associate with YB-1 was exciting for the laboratory, as YB-1 correlates to drug resistance in several cancers. Recognizing a new pathway opens new avenues for knowledge-based research and potential drug candidates.
“We conducted functional assays on one of these RNAs, and found that it had the ability to suppress cancer cell growth when it interacted with YB-1,” said co-senior author Donald B. DeFranco, PhD, a professor of pharmacology and chemical biology at Pittsburgh School of Medicine. “More work must be done to determine how these shyRNAs interact to influence cancer progression and perhaps influence other diseases.”
Expression of this one RNA, called Shad1, correlated to expression of YB-1, while inhibition of Shad1 led to increased cell proliferation. Since Shad1 fits into the category of shyRNAs, it is likely that additional shyRNAs influence prostate cancer cell proliferation. Examining shyRNAs and smyRNAs in-depth will provide a greater understanding of the mechanisms underlying prostate cancer development and progression.
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