Genome's dark matter offers clues to major challenge in prostate cancer

May 28, 2018, University of Michigan
Arul Chinnaiyan, M.D., Ph.D. Credit: Rogel Cancer Center

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 , a key player in prostate . 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 is published in Nature Genetics.

Current prostate cancer treatments aim to block the 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 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.

Chinnaiyan's lab identified thousands of lncRNAs in a 2015 paper. Long non-coding RNAs are considered the dark matter of the genome because so little is known about them.

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.

"At the end of the day, you're creating or stabilizing more androgen receptor signaling 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 tumor growth. In mouse models, elevating ARLNC1 caused large tumors to form. Knocking down ARLNC1 in mice caused tumors to shrink.

Researchers plan to continue studying the biology of ARLNC1 to understand how it's involved in progression and androgen receptor signaling.

"We want to further characterize the 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."

Explore further: A new method for prostate cancer imaging

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

Related Stories

A new method for prostate cancer imaging

July 21, 2016
Prostate cancer is one of the most common cancers in men. Tumor growth is critically regulated by the androgen receptor, and treatment strategies to lower androgens, such as testosterone, are a mainstay of clinical treatment. ...

New target for prostate cancer resistant to anti-hormone therapies

April 23, 2014
Prostate cancer becomes deadly when anti-hormone treatments stop working. Now a new study suggests a way to block the hormones at their entrance.

Gene fusions may be the 'smoking gun' in prostate cancer development

May 18, 2010
Prostate cancer treatments that target the hormone androgen and its receptor may be going after the wrong source, according to a new study. Researchers have found that when two genes fuse together to cause prostate cancer, ...

Study identifies new prostate cancer drug target

February 6, 2012
Research led by Wanguo Liu, PhD, Associate Professor of Genetics at LSU Health Sciences Center New Orleans, has identified a new protein critical to the development and growth of prostate cancer. The findings are published ...

Study identifies a key cellular pathway in prostate cancer

February 10, 2014
Mayo Clinic researchers have shed light on a new mechanism by which prostate cancer develops in men. Central to development of nearly all prostate cancer cases are malfunctions in the androgen receptor—the cellular component ...

Researchers find new co-regulator of the androgen receptor in prostate cancer

June 9, 2017
An international study led by University of Adelaide researchers has identified a new gene of interest linked to prostate cancer – and it's a gene with a split personality: it appears to play a major role in promoting cancer ...

Recommended for you

Treatment shown to improve the odds against bone marrow cancer

December 15, 2018
Hope has emerged for patients with a serious type of bone marrow cancer as new research into a therapeutic drug has revealed improved outcomes and survival rates.

Immunotherapy combo not approved for advanced kidney cancer patients on the NHS

December 14, 2018
People with a certain type of advanced kidney cancer will not be able to have a combination of two immunotherapy drugs on the NHS in England.

Scientists identify method to study resilience to pain

December 14, 2018
Scientists at the Yale School of Medicine and Veterans Affairs Connecticut Healthcare System have successfully demonstrated that it is possible to pinpoint genes that contribute to inter-individual differences in pain.

CRISPR joins battle of the bulge, fights obesity without edits to genome

December 13, 2018
A weighty new study shows that CRISPR therapies can cut fat without cutting DNA. In a paper published Dec. 13, 2018, in the journal Science, UC San Francisco researchers describe how a modified version of CRISPR was used ...

New drug seeks receptors in sarcoma cells, attacks tumors in animal trials

December 13, 2018
A new compound that targets a receptor within sarcoma cancer cells shrank tumors and hampered their ability to spread in mice and pigs, a study from researchers at the University of Illinois reports.

Noncoding mutations contribute to autism risk

December 13, 2018
A whole-genome sequencing study of nearly 2,000 families has implicated mutations in 'promoter regions' of the genome—regions that precede the start of a gene—in autism. The study, which appears in the December 14 issue ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.