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Eman Toraih

miR-196a2 oncomir and rs11614913 variant regulate signaling networks of cancer-associated biology

Cancer diagnosis and prognosis are affected by tumor molecular features. Identification of type-specific biomarkers is relevant to cancer translational research. MicroRNAs (miRNA) have been linked to cancer development and progression and the molecular mechanisms underlying the genetic associations of miRNA SNPs with cancer vary by cancer site. We aimed to determine the expression profile of mature miR-196a2 in various types of solid tumors and to analyze the impact of its polymorphism (rs11614913; C/T) on the expression levels. We worked upon 230 cancer patients (including 17 types of cancer) and 100 unrelated controls. Real-time polymerase chain reaction analysis was performed for allelic discrimination and relative quantification of miR-196a2 in cancer specimens. In silico target gene prediction and network analysis was executed. We found that individuals with T variant were associated with cancer risk under all genetic association models, especially in colorectal, esophageal, skin, lung, thyroid, and renal cancer. Overall and stratified analysis showed over-expression of miR-196a2 in most of our malignant tumor samples compared to their normal adjacent tissues. Carriers of C allele had significantly higher expression levels. Correlation with the clinicopathological features of cancer showed organ-specific effects. Gene enrichment analysis of predicted and validated targets speculated the putative role of miR-196a2 in cancer-associated biology. We highlighted a relevant and cancer-type specific expression for miR-196a2 and demonstrated that adding this type of microRNA marker to gene signatures and the clinicopathological features of various types of cancer could help for a better diagnosis and prognosis.