Posting again. Encouraging research.

[Jimbob9999]

ANN ARBOR, Michigan — 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 is published in Nature Genetics.

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 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 prostate cancer progression and androgen receptor signaling.

"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."

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Additional authors: Yajia Zhang, Sethuramasundaram Pitchiaya, Marcin Cieslik, Yashar S. Niknafs, Jean C-Y. Tien, Yasuyuki Hosono, Matthew K. Iyer, Sahr Yazdani, Shruthi Subramaniam, Sudanshu K. Shukla, Xia Jiang, Lisha Wang, Tzu-Ying Liu, Michael Uhl, Alexander R. Gawronski, Yuanyuan Qiao, Lanbo Xiao, Saravana M. Dhanasekaran, Kristin M. Juckette, Lakshmi P. Kunju, Xuhong Cao, Utsav Patel, Mona Batish, Girish C. Shukla, Michelle T. Paulsen, Mats Ljungman, Hui Jiang, Rohit Mehra, Rolf Backofen, Cenk S. Sahinalp, Susan M. Freier, Andrew T. Watt, Shuling Guo, John T. Wei, Felix Y. Feng, Rohit Malik

Funding: National Institutes of Health grants P50CA186786, U01 CA214170, DP5 OD012160; Prostate Cancer Foundation; Howard Hughes Medical Institute; American Cancer Society; University of Michigan Taubman Institute; U.S. Department of Defense grants W81XWH-13-1-0284, W81XWH-17-1-0134, W81XWH-16-1-0314; W81XWH-16-1-0195, W81XWH-14-1-0508, W81XWH-14-1-0509; AACR-Bayer Prostate Cancer Research Fellowship 16-4-044-PITC; German Research Foundation BA2168/11-1 SPP1738

Disclosure: The University of Michigan has filed a patent on lncRNAs as biomarkers of cancer and Chinnaiyan is named as an inventor. Chinnaiyan is a co-founder of LynxDx, which is developing lncRNA biomarkers.

Reference: Nature Genetics, doi: 10.1038/s41588-018-0120-1, published May 28, 2018

[CalBear74]

Thank you for this update. This is a very exciting line of research for patients like myself. God Speed to all these physicians, microbiologists, and pathologists.

[vandy69]

Good Tuesday Morning Jimbob9999,

I have been in this battle for almost six years. News like this gives me the will to fight on, with the hope that if I live long enough I may be saved by new technologies and treatments.

Thanks for posting.

Best wishes. Never Give In.

Mark, Atlanta

[Hidden]

definition of gene: "(in technical use) a distinct sequence of nucleotides forming part of a chromosome, the order of which determines the order of monomers in a polypeptide or nucleic acid molecule which a cell may synthesize."

That is, a portion of DNA that codes for systhesis of a protein (via creation of mRNA).

The lead to the article says:

"a novel gene they named ARLNC1 that controls signals from the androgen receptor"

What is "a signal from the androgen receptor". How does the AR send out "signals", except via synthesized proteins? For example, the AR does not have a radio transmitter.

So this segment, ARLLNC1, controls (inhibits) expression of a gene..

Genes are preceded by promoter regions and by inhibitor regions.

Is this what they are talking about? It's not that clear.

If it is, then the next gene down is the significant section. This ARLNC1 inhibits synthesis of the protein coded by the next gene down. What is that protein? They must have some idea, you would think.

What did you make of it?

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This statement is less than straight forward;

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

"Prostate cancer progression" and also "androgen receptor signaling"?

Are these two unrelated things? "A" and "B".

The thrust of the the argument would have to be that "B" causes "A". The only reason that "B" is interesting is because of "A". I dont think that they can hope to investigate "A" except by investigating "B".

I don't think they are making an effort to be clear.

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"dark matter". Pfft. Dark Ages.