Junk DNA Could Be Powerful Prostate Cancer Drug Target
The androgen receptor (AR) is key in the development of a healthy prostate as well as prostate cancer. This makes it an important target for therapies, “The androgen receptor is an important target in prostate cancer. Understanding that target is important. This study identifies a feedback loop that we could potentially disrupt as an alternative to blocking the androgen receptor directly,” says study senior author Arul Chinnaiyan, M.D., Ph.D., director of the Michigan Center for Translational Pathology.
Rather than study variants of AR directly, the study carried out a comprehensive RNA-seq profiling investigation of AR-regulated, cancer-associated, long noncoding RNAS (lncRNAs) from prostate cancer cell lines and patient tissue samples. The team found that ARLNC1 (a lncRNA producing gene) had an elevated expression level in prostate cancer. After further investigation it was found that the transcript is involved in a feedback look with the androgen receptor.
“At the end of the day, you’re creating or stabilizing more androgen receptor signalling in general and driving this oncogenic pathway forward. We’re envisioning a potential therapy against ARLNC1 in combination with therapy to block the androgen receptor – which would hit the target and also this positive feedback loop,” Chinnaiyan says.
When researchers blocked ARLNC1 in cell lines expressing androgen receptor, it led to cancer cell death and prevented tumour growth. In mouse models, elevating ARLNC1 caused large tumours to form. Knocking down ARLNC1 in mice caused tumours to shrink.
Researchers plan to continue studying the biology of ARLNC1 to understand how it’s involved in prostate cancer progression and androgen receptor signalling.
“We want to further characterize the dark matter of the genome,” Chinnaiyan says. “There are a number of these lncRNAs that we don’t understand how they functionally work. Some of them will certainly be very useful as cancer biomarkers and we think a subset are important in biological processes.”