Prostate cancer: a new target
Researchers from the University of Michigan (University of Michigan Rogel Cancer Center) have identified the ARLNC1 gene, which regulates the work of androgen receptors. These receptors play a key role in the development of prostate cancer. Knockout (shutdown) of the long non-coding RNA (lncRNA) gene controlling the expression of ARLNC1 led to the death of cancer cells in mice.
Existing methods of prostate cancer treatment are aimed at blocking the androgen receptor. Unfortunately, very often patients develop resistance to androgen-specific therapy. The disease flows into a more complex form – metastatic castration-resistant prostate cancer.
This study identifies a feedback mechanism that could be a potential target as an alternative to treatment based on blocking the androgen receptor directly.
lncRNAs are called the "dark matter" of the genome because they are poorly understood. In the process of searching for those lncRNAs that may play a role in the progression of prostate cancer, scientists found that the level of ARLNC1 protein in cancer cells is increased compared to a benign prostate tumor. This suggested their important role in the development of cancer. In addition, this protein has been linked to the androgen receptor signaling pathway.
Androgen receptors induce the expression of ARLNC1, which, in turn, binds to the matrix RNA containing information about the structure of the androgen receptor protein. This leads to the stabilization of the receptor, which again induced the expression of ARLNC1. The circle of positive feedback closes, as a result, the number of ARLNC1 and androgen receptors increases, tumor growth occurs.
Drugs targeting ARLNC1 in combination with drugs blocking the androgen receptor may prove to be an effective treatment for prostate cancer.
The researchers conducted a series of experiments in vitro and in vivo. Blocking of ARLNC1 in cell lines led to the death of cancer cells and the cessation of tumor growth. In mouse models, an increase in the expression of ARLNC1 caused the formation of large tumors, and suppression of the synthesis of this protein was accompanied by a decrease in the number of cancer cells.
The authors plan to continue studying ARLNC1 and understand what is the mechanism of its influence on the progression of prostate cancer and the transmission of androgen receptor signals.
Article by Y. Zhang et al. Analysis of the androgen receptor–regulated lncRNA landscape identifies a role for ARLNC1 in prostate cancer progression published in the journal Nature Genetics.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of the University of Michigan: Genome's Dark Matter Sheds Light on Prostate Cancer Challenge.