Dual biomarkers long non-coding RNA GAS5 and microRNA-34a co-expression signature in common solid tumors

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.

lncRNA GAS5 regulates myocardial infarction by targeting the miR‐525‐5p/CALM2 axis

“…Other studies investigated and demonstrated more than 15 lncRNAs involved in regulation of hypertrophy‐related disease genes . Among these lncRNAs, GAS5 was firstly studied in different types of cancers and the previous data proved the downregulated expression of GAS5 in cancer and serves as a tumor suppressor gene . However, its expression and biological role in MI is still limited.…”

“…10,22 Among these lncRNAs, GAS5 was firstly studied in different types of cancers and the previous data proved the downregulated expression of GAS5 in cancer and serves as a tumor suppressor gene. 12,13,15 However, its expression and biological role in MI is still limited. Yin et al proved that GAS5 was downregulated in coronary artery disease and it plays important role as upstream regulator of the mTOR signaling pathway in the development of CAD.…”

“…lncRNAs served role in origination and progression of cardiac disease through transcriptional and posttranscriptional control and binding with different microRNAs (miRNAs) as their target . As an lncRNA, growth arrest‐specific 5 (GAS5), has been reported plays a tumor suppressor role in different types of cancer though inhibition of tumor cell growth . In addition, GAS5 was also explored as a biomarker in coronary artery disease and its expression was downregulated in plasma of human hypertensive patients and in the arteries and retina of rat model .…”

“…7,10 As an lncRNA, growth arrest-specific 5 (GAS5), has been reported plays a tumor suppressor role in different types of cancer though inhibition of tumor cell growth. [11][12][13] In addition, GAS5 was also explored as a biomarker in coronary artery disease and its expression was downregulated in plasma of human hypertensive patients and in the arteries and retina of rat model. 14,15 However, its expression profile and biological function in MI is still largely unknown.…”

Overexpression of long noncoding RNA GAS5 suppresses tumorigenesis and development of gastric cancer by sponging miR-106a-5p through the Akt/mToR pathway

“…GAS5 has been reported to be aberrantly expressed in some cancers, including lung cancer (Wu et al, 2016(Wu et al, ), cervical cancer (W et al, 2014, breast cancer(GT 2016) and gastric cancer and function important roles in cell processes, such as proliferation, invasion, migration and apoptosis. Growing studies have disclosed the functional mechanism of lncRNAs in tumorigenesis by sponging specific miRNAs because of their direct interaction are attracting multi-field researchers' attention (Ke et al, 2018, Toraih et al, 2018. However, the roles and potential mechnisms of GAS5 in GC are still not well clarified yet.…”