A group of researchers at Virginia Commonwealth University (VCU) Massey Cancer Center and VCU Institute of Molecular Medicine (both VA, USA) have identified a novel interaction between a microRNA and a gene, a finding that could lead to the development of new treatments for malignant glioma. The study, led by Luni Emdad and Paul Fisher (both VCU Institute of Molecular Medicine and VCU Massey Cancer Center) was published recently in the journal Neuro-Oncology.
The research identified a link between a microRNA, miR-184, and a cancer-promoting gene, SND1, in the regulation of malignant glioma. miR-184 is known to suppress tumor development by regulating cancer growth genes, while SND1 is associated with the development of various cancers including those of the breast, colon, prostate and liver. The team demonstrated that increasing the expression of miR-184 slows the growth and invasiveness of glioma cells through direct regulation of SND1. They also demonstrated that reduced levels of SND1 led to reduced levels of STAT3, a gene that has been linked to the promotion of the most lethal characteristics of this brain cancer.
“Patients suffering from brain tumors are in desperate need of improved therapies,” explained Fisher. “We’re hopeful that this new understanding of the relationship between miR-184 and SND1 ultimately will lead to the development of new drugs that reduce SND1 expression and improve patient outcomes.”
It is known that levels of miR-184 are remarkably low in malignant glioma tissue samples. Using advanced computer analysis techniques, the researchers identified SND1 among a small number of genes that miR-184 helps regulate. The team confirmed low levels of miR-184 expression in human glioma tissue samples and cultured cell lines, as well as an increase in the expression of SND1 compared with normal brain tissue. Using data from REMBRANDT, a public brain tumor database, it was confirmed that lower levels of SND1 are linked to longer survival.
“We still have a long way to go and many challenges to overcome before we will have therapies that are ready for clinical use, but this is a significant first step in the process,” commented Emdad.”Future studies will aim to explore the relationship between SND1 and STAT3, identify additional microRNAs that may be relevant to malignant glioma and explore the effects of drugs that block SND1 expression in more advanced preclinical models.”
Source: Emdad L, Janjic A, Alzubi MA et al. Suppression of miR-184 in malignant gliomas upregulates SND1 and promotes tumor aggressiveness. Neuro-Oncology, doi: 10.1093/neuonc/nou220 (2014) [Epub ahead of print].