Abstract

Decrypting the microRNA signatures in gastric cancer using high-throughput miRNA array coupled with systems biological approaches for precision medicine

Author(s): Fehmida Bibi, Peter Natesan Pushparaj, Muhammad I. Naseer, Muhammad yasir, Esam I. Azhar

MicroRNAs (miRNAs) are non-coding small RNA molecules that regulate the differential expression of genes. The expression of miRNAs is dysregulated in various types of cancers, including Gastric Cancer (GC), and has both prognostic and diagnostic potential. To interpret the role of miRNA expression in GC, we evaluated the expression profile using high-throughput miRNA array followed by in-depth systems biological analyses. Total RNA was isolated from 34 GC patients and 15 normal controls and hybridised and differentially expressed miRNAs in GC compared to normal controls were analysed. A total of 250 miRNAs were found to be differentially expressed in GC with a fold change ranging from + 2.5984 to – 3.5271 compared to normal gastric tissues. The differentially expressed miRNAs were further subjected to Ingenuity Pathway Analysis to understand the modulation of cellular and molecular functions and associated physiological system development and functions in GC. The Oncomirs such as miR-155-5p, miR-17-5p, miR-21-5p, miR-23a-3p, miR-24-3p, and miR-320b were significantly (P<0.05) upregulated and all the other miRNAs, mostly tumor suppressors, were significantly downregulated (P<0.05) leading to the reduction in cell death and the induction of gastric cancer, cellular growth and proliferation, cellular movement, cellular assembly and organization, DNA replication, recombination and repair, organismal injury and abnormalities and metastasis of tumor in GC compared to normal tissues. The high-throughput miRNA microarray coupled with systems biological analyses showed that miRNAs are dysregulated in GC, causing the initiation, progression, and metastasis of GC. In conclusion, the novel GC-inducing miRNA signatures decrypted in our study can further be exploited for precision medicine in clinics.

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