The Myc-Regulated Long Noncoding RNA DANCR in Prostate Cancer
Abstract
This application is in response to the overarching challenge: Distinguish aggressive from indolent disease in men newly diagnosed with prostate cancer. Changes in DNA sequence and gene expression drive prostate cancer growth. The human genome is made up of deoxyribonucleic acid (DNA) contained in our cells. Our DNA is made up of six billion individual DNA "letters," which are packaged into chromosomes. Just like the letters in a book make up words to tell a story, so do the letters in our genomes, which make up genes that ultimately produce proteins. These proteins can control cell division and comprise of proteins that serve as "accelerators" that increase cell replication or "brakes" that slow down growth. The accelerators are known as "oncogenes," and the brakes as "tumor suppressors." In prostate cancer cells, small changes in these genetic letters can significantly alter what a genomic word or sentence means. For example, a change in a single letter can lead to the production of a protein accelerator that is stuck and is always turned on, resulting in cancer cell growth. Prostate cancer is a genetic disease involving multi-step changes in the genome that destroy brakes and cause accelerators to be stuck. By studying the prostate cancer genome, scientists can discover what letter changes are causing a cell to become cancerous. One of the best known examples is the discovery of the androgen receptor mutation (i.e., a change of the nucleotide sequence of androgen receptor gene) in patients, allowing for the development of new therapies. Studies to identify genetic drivers in prostate cancer have been focused mainly on protein-coding genes. The sequence of a gene (DNA) is transcribed to a ribonucleic acid (RNA) sequence that, in turn, instructs the assembly of a particular protein from amino acids. There are two major steps to go from DNA to protein: (1) the DNA on which the gene resides is transcribed from DNA to RNA (a process termed "transcription"), and the RNA is then translated into a protein (a process called "translation"). Protein-coding RNA (also called messenger RNA; mRNA) therefore serves as an "intermediate language" in the translation of a gene s message into a protein s amino acid sequence. In contrast, non-coding RNA refers to a functional RNA molecule that is not translated into a protein. Before the discovery of non-coding RNA genes in cancer, the search for novel genes that drive the development of cancer was focused mainly on protein-coding genes (which make mRNAs) that reside in recurrent alterations in cancer genomes. However, in prostate cancer genomes, it was determined that many of these recurrent alterations were located in protein-coding gene "desert" regions or "junk" DNA. The lack of protein-coding genes in cancer-associated genetic alterations is further supported by the fact that only 2% of the human genome contains instructions for making ~25,000 proteins, while over 30% of the genome is altered in cancer. These findings, in combination with the recent revelation that about 70% of the human genome is transcribed into RNA (as compared to only 2% that is transcribed to mRNA), strongly suggest that non-coding RNAs may play significant roles in prostate tumor development. Long non-coding RNAs are a new class of cancer-driving genes with translational potential in prostate cancer. Seventy percent of the human genome is transcribed into RNA, yielding many thousands of non-coding RNAs. The recent discovery of long non-coding RNA (lncRNA) genes may dramatically change our understanding of prostate cancer. LncRNAs are defined as RNA molecules larger than 200 nucleotides or letters that do not appear to code for proteins. Several lncRNAs have been shown to behave as oncogenes or tumor suppressors in prostate cancer. Thus, the study of lncRNAs is at the cutting edge of cancer research. Investigation of the functions of lncRNAs in cancer will lead to a greater understand
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 29, 2016
- Source ID
- W81XWH1510630
Entities
People
- Chi Dang
Organizations
- United States Army
- University of Pennsylvania