To help glioblastoma multiforme patients, researchers at the University of Illinois at Urbana-Champaign have taken an unusual approach to studying the role of microRNAs in this deadly brain cancer. By evaluating 534 miRNAs simultaneously — instead of one at a time as is typically done — the team confirmed 25 miRNAs previously associated with glioblastoma survival and found 20 miRNAs associated with breast cancer, ovarian cancer, and gastric adenocarcinoma tumor growth.
"If you look at one microRNA alone, it may appear to be related to cancer, but the relationship may be indirect — through another microRNA. So only by looking at all microRNAs can we truly find the association between each microRNA, taking into account all others," says Sandra Rodriguez Zas at Urbana-Champaign. "The challenge comes from the number of patients with survival and microRNA information relative to the number of microRNAs — you need to have many patients, observations, per microRNA in order to accurately and precisely conclude if the microRNA is associated with survival."
To meet these challenges, Zas and her group developed a bioinformatics pipeline that allows them to look at all miRNAs, remove those that are not associated with the disease, and still look at multiple miRNAs to establish which ones are related to cancer survival.
The researchers hope that drug therapies capable of boosting or repressing expression of the target genes, or the miRNAs that control the expression of those target genes, can be developed based on their lists of miRNAs. "One especially helpful aspect of our study is, because we are studying multiple microRNAs and their target genes, that the chances to develop an effective drug therapy based on our results increase. We are looking at the whole picture and the therapy development process can consider all components and their synergistic and antagonistic interactions," Zas says.
She and Kristin Delfino, a doctoral candidate at Urbana-Champaign, are now extending this approach to ovarian cancer survival. The extension includes the consideration of transcription factors, the identification of interaction between miRNAs, transcription factors, and gene targets for the development of additional therapies to fight this disease.