Genetic Variations in DNA Could Help Improve Efficacy of Clinical Trials


Source: University of Michigan

Summary: Researchers identified a novel gene that controls signals from the androgen receptor, a key player in prostate cancer.


Current prostate cancer treatments aim to block the androgen receptor to stop cancer growth. But most patients become resistance to androgen-specific therapies, developing a challenging form of the disease called metastatic castration-resistant prostate cancer. The dark matter of the human genome may shed light on how the hormone androgen impacts prostate cancer. Researchers at the University of Michigan, Rogel Cancer Center identified a novel gene they named ARLNC1 that controls signals from the androgen receptor, a key player in prostate cancer. Knocking down this long non-coding RNA in mice led to cancer cell death, suggesting this may be a key target for future therapies. The study findings were published in the journal Nature Genetics.

Cancer of the prostate glands

Arul Chinnaiyan, M.D., Ph.D. Credit: Rogel Cancer Center

While searching for lncRNAs that might play a role in prostate cancer, the team discovered that ARLNC1 is elevated in prostate cancer relative to benign prostate tissue, which suggests a role in cancer development. And it was associated with androgen receptor signaling, which made it more intriguing. The researchers found that the androgen receptor actually induces ARLNC1 expression. Then ARLNC1 binds to the androgen receptor messenger RNA transcript. This stabilizes the level of androgen receptor, which then feeds back to sustain ARLNC1. They plan to continue studying the biology of ARLNC1 to understand how it’s involved in prostate cancer progression and androgen receptor signaling.

Senior author, Dr. Arul Chinnaiyan said, “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.”


More Information: Yajia Zhang et al, “Analysis of the androgen receptor-regulated lncRNA landscape identifies a role for ARLNC1 in prostate cancer progression”, Nature Genetics (2018). DOI: 10.1038/s41588-018-0120-1 


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