Looking at the Big Picture
“Historically, investigators have frequently focused on specific genes or pathways but are now realizing that the whole transcriptome, as opposed to single genes, may be involved in any response,” says Hua Lu, M.D., Ph.D., professor and chair of biochemistry and molecular biology at Tulane University School of Medicine.
Researchers in Dr. Lu’s lab recently described and characterized inauhzin, a small molecule that activates and stabilizes p53 by increasing its acetylation and, as a result, suppresses tumor growth. Microarray analyses combined with RT-qPCR performed by Dr. Lu and colleagues revealed that the induction of p53 target genes occurs at a much larger scale than previously thought.
Over 320 genes were overexpressed at least 2.3-fold, and over 260 genes were downregulated at least twofold by inauhzin, in a p53-dependent manner. “This finding provided opportunities to see more genes that are involved, globally, in the p53 response, and to obtain a much better image than by examining a single pathway,” says Dr. Lu.
This strategy also unveiled multiple genes that are regulated by inauhzin in a p53-independent manner. “This is what should be done when examining a drug, to understand the response, because a number of classical drugs have been revealed to have additional targets,” explains Dr. Lu.
Reaping the benefits of technological advances, transcriptomics is catalyzing the emergence of new paradigms in molecular and clinical oncology. The increasing focus on surveying global cellular perturbations, and the integration of the data with other systems-level approaches, including genomics and proteomics, define new conceptual frameworks.
These interdependent technological and research developments are paving the path toward the time when the systematic analysis of cancer transcriptomes, still in its infancy, will become a routine part of clinical medicine.