A study led by researchers at the University of Pittsburgh School of Medicine in Pennsylvania recently revealed that specific noncoding RNA molecules can play a role in prostate cancer development, the second most common cancer in men. The study is entitled “Noncoding RNAs that associate with YB-1 alter proliferation in prostate cancer cells” and was recently published in the journal RNA.
The expression levels of the human Y-box binding protein 1 (YB-1), a highly conserved and multifunctional protein known to promote cellular proliferation, have been reported to correlate with drug resistance and poor clinical outcomes in several types of cancer. In breast cancer in particular, YB-1 was considered to be a powerful prognostic indicator. Now, YB-1 was found to be associated to a class of RNAs linked to cancer.
“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,” explained the study’s co-senior author Dr. Bino John in a news release. “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.”
MicroRNAs are small non-coding RNA molecules able to regulate gene expression. In the study, researchers discovered that YB-1 associates with several microRNAs, and that remarkably, thousands of these microRNAs had not been reported before. The team divided RNAs into two classes: YB-1 associated short non-coding RNAs (shyRNAs) and their further processed small RNAs (smyRNAs).
Curiously, one of the new RNAs was found to originate from the gene Dicer 1, which encodes an important protein for the production of microRNAs. Dicer1 was found to colocalize in cells with YB-1, and their expressions were reported to correlate to each other, suggesting an interaction between the two.
“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 the study’s co-senior author Dr. Donald B. DeFranco. Dicer was also found to control the expression of several genes involved in cancer progression, namely DLX2 and IGFBP2 genes.
The team concluded that YB-1 is closely associated to microRNAs that can play a role in prostate cancer progression. The team suggests that further studies should be conducted to better understand the role of these noncoding RNAs in a cancer context. “More work must be done to determine how these shyRNAs interact to influence cancer progression and perhaps influence other diseases.” concluded Dr. DeFranco.