From a team at the UC Davis Comprehensive Cancer Center, a series of studies has shown that a single molecule is at the heart of one of the most basic survival tactics of prostate cancer cells.
A paper published today by the Public Library of Science identifies a microRNA called miR-125b as a potential target for treatments designed to stop the proliferation of prostate cancer cells, particularly in patients who have developed a late-stage form of the disease resistant to androgen deprivation therapy.
MicroRNAs are small, single strands of RNA that regulate gene expression processes between larger strands of RNA - that is, they play vital roles in turning genes on and off. RNA, or ribonucleic acid, is a family of large molecules involved in the coding, decoding, regulation and expression of genes.
"Our latest research demonstrates that elevated MiR-125B in prostate cancer cells is a mechanism that thwarts our efforts to eradicate the disease," said de Vere White.
The UC Davis study details exactly how miR-125b represses a protein called p14ARF in two prostate cancer cell lines and in a mouse model. The study is important because it is the first to identify miR-125b as a direct regulator of p14ARF in metastatic prostate cancer cells.
P14ARF is an important link in the pathway between two genes that suppress prostate cancer cells, p53 and PUMA. When miR-125b down regulates p14ARF, p53 is restrained from its job of killing cancer cells. Treatment of prostate cancer cells with an inhibitor of miR-125 results in increased expression of p14ARF and full functioning of p53, leading to the death of prostate cancer cells, known as apoptosis, and a concomitant slowing tumor growth.
This is known as a p53-dependent pathway; there's also a p53-independent pathway, and miR-125b down regulates that as well. Thus this paper shows that, through its manipulation of p14ARF, miR-125b is a major modulator of cell death, whether p53-dependent or independent. Since all prostate cancer cells are one or the other, this phenomenon impacts all of them, which makes miR-125b an important molecule in the progression of prostate cancer.
"These latest findings reinforce our belief that miR-125b has potential as a therapeutic target for the management of patients with metastatic prostate cancer," said deVere White. "We're pleased that these data build so successfully on our earlier studies of miR-125b and bring us closer to patient treatment."
Other authors were Sumaira Amir, Ai-Hong Ma, Xu-Bao Shi, Lingru Xue, Hsing-Jien Kung, all of the UC Davis School of Medicine. The study was supported by grants from the National Cancer Institute (CA136597) and Department of Defense (PC080488).