Oncogenomics Shared Resource Facilitates the Study of the "Other" Nucleic Acid in Cancer Biology
Advancements in DNA sequencing technology now allow cancer researchers to easily probe the intricate details of the genomes of cancer cells. In addition to identifying specific genetic alterations in cell DNA, sequencing methods can now provide a quantitative analysis of the “other” nucleic acid — RNA, which is produced by all living cells.
Utilizing the expertise of the Oncogenomics Shared Resource, a core co-managed by the UF Health Cancer Center and the Interdisciplinary Center for Biotechnology Research, Cancer Center researchers use RNASeq as a tool to investigate the molecular processes occurring in cells that lead to the cancer pathological state.
In the central dogma of biology, DNA makes RNA which makes proteins. Because it can be technically difficult to measure all of the proteins made by a cell, RNA can serve as a surrogate marker for protein. The total population of RNA synthesized (transcribed) from the DNA gene template is called the transcriptome. RNA can be extracted in pure form from cancer cells, readily converted into DNA in the test tube and then sequenced using conventional DNA sequencing technology.
The process of analyzing the RNA transcriptome by DNA sequencing is called RNASeq. The ability to measure the activity of genes that may be active in cancer cells can provide insight into the molecular mechanism of tumor development and offer a clue as to which anti-cancer drug may be the best to use in fighting the particular tumor type.
Christian Jobin, Ph.D., professor of medicine and co-leader of the Cancer Therapeutics and Host Response Program, studies the role of intestinal bacteria in the development of inflammatory bowel diseases and colorectal cancer. Using mice models of human colorectal cancer, Dr. Jobin studies the differential contribution of bacteria in protecting or exacerbating the development of colitis and colorectal cancer.
RNASeq is an important technology used by Dr. Jobin for identifying key changes in gene expression — both in the gut microorganisms and in human intestinal cells. It is a way to understand the cellular and molecular mechanisms regulating host response to bacterial colonization, how these impact intestinal homeostasis and may trigger tumor formation.
“The expertise of the Oncogenomic Core in RNA-seq is essential to our understanding of how microbial and host transcriptomic response influence carcinogenesis,” Jobin said.
RNA can come in several ‘flavors,” and each has a specific function in the cell. Messenger RNA, or mRNA, serves as the intermediary molecule that transfers the genetic instructions in the DNA (the gene) to the cellular protein synthesis machinery (the ribosome). Without mRNA, cells could not make the necessary proteins required for life. Transfer RNA, or tRNA, is vital for facilitating the ability of the ribosome to interpret the information pertaining to protein sequence that is contained in the mRNA molecule, while ribosomal RNAs, or rRNAs, provide the structural integrity of the ribosome.
Other small cellular RNAs are involved in converting mRNA into the proper format for recognition by ribosomes. Even smaller “microRNAs” play a critical role in modulating the cytoplasmic levels of mRNAs, thereby affecting protein production. A new large class of RNAs called long non-coding RNAs or lncRNAs, do not code for proteins but are involved in a surprisingly wide variety of cellular functions, including turning genes on and off, and have been associated with human diseases such as cancer, Alzheimer’s disease and heart disease.