Endocrine Abstracts

Introduction: Prostate cancer is the most prevalent malignancy affecting Western males. Initially an androgen-dependent disease, androgens bind to the androgen receptor and drive expression of genes that promote proliferation and evasion of apoptosis. Although advanced disease involves reduced androgen dependence, androgen receptor signalling remains a key driver of growth. Androgen deprivation therapy (ADT) is first line, but resistance inevitably develops. A...

A key mechanism of persistent cell survival under testosterone suppression in advanced prostate cancer (PC) is continued Androgen Receptor (AR) activation. This results from AR mutation, overexpression, hyper-activation, and/or expression of constitutively-active AR transcript variants (AR-Vs). AR has an unusually long 3’ untranslated region (3’UTR), which performs vital regulatory roles but is remarkably understudied. Its contribution to continued AR activation unde...

Prostate cancer is an androgen dependent malignancy that initially responds well to androgen ablation therapy. However treatment, castrate resistant prostate cancer eventually emerges. Even in that phase of the disease, the androgen receptor (AR) still seems to play a role. MicroRNAs are small (19–25nt) non-coding RNAs that modulate gene silencing through inhibition of translation and mRNA degradation. They are considered to be master regulators of gene expression and act...

Prostate Cancer (PC) affects 1-in-6 men in the UK, and obesity 1-in-3, with rates of both increasing. High-fat diet is linked with increased risk of PC death, and volume of peri-prostatic adipose tissue (PPAT) is associated with increased risk of lethal PC/reduced therapy response. Despite this, molecular mechanisms underpinning obesity-driven PC remain poorly-understood. This is important since weight-gain and central obesity are major side-effects of PC trea...

Androgens initially drive prostate tumour growth. Although in advanced disease there is no longer dependence on circulating androgens, the androgen receptor (AR) remains a key driver of this lethal stage thus new ways to inhibit its activity are required. MicroRNAs play vital roles in prostate cancer (PCa) development, progression and metastasis. Previous studies have examined microRNAs dysregulated in PCa, and also identified androgen-regulated microRNAs. We approached microR...

MiR-346 is an Androgen Receptor (AR)-activating miR that associates with DNA damage response (DDR)-linked transcripts in prostate cancer (PC). MiR-346 induces rapid and extensive DNA damage in PC cells through chromatin association, activation of transcription, R-loop formation and DNA replication stress, leading to checkpoint activation and cell cycle arrest. MiR-346 interacts with lncRNA, NORAD, in PC cells, which functions to maintain mitosis, DDR, and chromosomal integrity...