Long noncoding RNA-mediated activation of androgen receptor in prostate cancer

Abstract

Remarkable progress has been made in molecular characterization of prostate cancer (PCa) with continued innovations in high throughput technologies evaluating human cancer. Since the completion of the Human Genome Project it has been estimated that only about 1.5%–2% of our genome codes for proteins. Various genome-wide approaches, e.g. the ENCODE project, revealed that a much larger percent of the genome is transcribed as non-protein coding (nc) RNA, including long noncoding (lnc) RNA (over 200 bps long). Although the biological roles of lncRNA (the ‘dark matter of the genome’) are not nearly as well-understood as the protein coding mRNAs, it is increasingly clear that they play important roles in almost every aspects of biology, including cancer biology. This is exemplified by recent genome-wide association studies revealing that over 80% of cancer-associated single nucleotide polymorphisms (SNPs) are in noncoding regions of the genome.

Figure 1

Schematic model illustrating AR (red dimer on DNA) activation by overexpressed lncRNAs PCGEM1 and PRNCR1(blue ribbons) in prostate tumors. The increased thickness of the red arrow represents elevated mRNA expression of AR-regulated genes. AR: androgen receptor.