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Published on: November 28, 2018
Dual biomarkers long non-coding RNA GAS5 and microRNA-34a co-expression signature in common solid tumors
Eman A Toraih1,2, Saleh Ali Alghamdi3, Aya El-Wazir1,2
1Genetics Unit, Department of Histology and Cell Biology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
Abstract:
Accumulating 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), glioblastoma (GB), and hepatocellular carcinoma (HCC) 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. The tumor suppressor lncRNA GAS5 was significantly under-expressed in the three types of cancer [0.08 (0.006-0.38) in RCC, p <0.001; 0.10 (0.003-0.89) in GB, p < 0.001; and 0.12 (0.015-0.74) in HCC, p < 0.001]. 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]. Consistent to the computationally predicted miRNA-lncRNA interaction, negative correlations were observed between levels of GAS5 and miR-34a in RCC samples (r = -0.949, p < 0.001), GB (r = -0.518, p < 0.001) and HCC (r = -0.455, p = 0.013). Kaplan-Meier curve analysis revealed that RCC patients with down-regulated miR-34a levels had significantly poor overall survival than their corresponding (p < 0.05). Hierarchical clustering analysis showed RCC patients could be clustered by GAS5 and miR-34a co-expression profile. Our results suggest potential applicability of GAS5 and miR-34a with other conventional markers for various types of cancer. Further functional validation studies are warranted to confirm miR-34a/GAS5 interplay in cancer.
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