The androgen receptor (AR) acts in prostate cancer not only as a transcriptional activator, but also as a direct repressor of the nuclear receptor LRH-1 (NR5A2). This is the conclusion of a new study published in the journal Genes & Diseases .

LRH-1 is involved in metabolic processes and intratumoral steroidogenesis and promotes tumor growth in the castration-resistant form of prostate cancer (CRPC). The study now shows that the AR under the influence of androgens directly suppresses LRH-1 via a specific chromatin loop structure.

The researchers found that AR occupies a distal enhancer about 140 kilobases downstream of the NR5A2 transcription starting point. In the presence of androgens, a long chromatin loop is formed, which connects this enhancer to the promoter. As a result, AR recruits corepressors such as ERG, EZH2 and histone deacetylases (HDACs), resulting in epigenetic silencing of LRH-1.

During androgen deprivation, as occurs with androgen deprivation therapy (ADT), this repressive loop dissolves, resulting in severe overexpression of LRH-1. This contributes to the progression of the disease.

The authors see the AR-LRH-1 axis as a new regulatory mechanism in prostate cancer development. In the future, a targeted influence on this interaction could enable new therapeutic approaches for advanced and castration-resistant prostate cancer.

The study was conducted by researchers from the Chinese University of Hong Kong, Southern Medical University and Sun Yat-sen University and supported by several Chinese and Hong Kong funding institutions.

Oiginal Paper:

Androgen receptor acts as the transcriptional repressor of the nuclear receptor LRH-1 via the androgen-driven chromatin looping conformation in prostate cancer – ScienceDirect

Editor: X-Press Journalistenbüro GbR

Gender Notice. The personal designations used in this text always refer equally to female, male and diverse persons. Double/triple naming and gendered designations are used for better readability ected.