Molecular analysis of long non-coding RNA GAS5 and microRNA-34a expression signature in common solid tumors: A pilot study

Abstract

AbstractAccumulating evidence indicates that non-coding RNAs including microRNAs (miRs) and long non-coding RNAs (lncRNAs) are aberrantly expressed in cancer, providing promising biomarkers for diagnosis, prognosis and/or therapeutic targets. We aimed in the current work to quantify the expression profile of miR-34a and one of its bioinformatically selected partner lncRNA growth arrest-specific 5 (GAS5) in a sample of Egyptian cancer patients, including three prevalent types of cancer in our region; renal cell carcinoma (RCC), hepatocellular carcinoma (HCC) and glioblastoma (GB) as well as to correlate these expression profiles with the available clinicopathological data in an attempt to clarify their roles in cancer. Quantitative real-time polymerase chain reaction analysis was applied. Different bioinformatics databases were searched to confirm the potential miRNAs-lncRNA interactions of the selected ncRNAs in cancer pathogenesis. GAS5 was significantly under-expressed in the three types of cancer. However, levels of miR-34a greatly varied according to the tumor type; it displayed an increased expression in RCC [4.05 (1.003-22.69),p<0.001] and a decreased expression in GB [0.35 (0.04-0.95),p<0.001]. A weak negative correlation was observed between levels of GAS5 and miR-34a in GB [r = −0.39,p=0.006]. Univariate analyses revealed a correlation ofGAS5downregulation with poor disease-free survival (r = 0.31,p=0.018) and overall survival (r = 0.28,p=0.029) in RCC but not in GB, and a marginal significance correlation with a higher number of lesions in HCC. Hierarchical clustering analysis showed RCC patients among others, could be clustered by GAS5 and miR-34a co-expression profile. Our results confirm the tumor suppressor role of GAS5 in cancer and suggest its potential applicability to be a predictor of bad outcomes with other conventional markers for various types of cancer. Further functional validation studies are warranted to confirm miR-34a/GAS5 interplay in cancer.