Integrative network analysis reveals active microRNAs and their functions in gastric cancer

Abstract

BackgroundMicroRNAs (miRNAs) are a class of endogenous, small and highly conserved noncoding RNAs that control gene expression either by degradation of target mRNAs or by inhibition of protein translation. They play important roles in cancer progression. A single miRNA can provoke a chain reaction and further affect protein interaction network (PIN). Therefore, we developed a novel integrative approach to identify the functional roles and the regulated PIN of oncomirs.ResultsWe integrated the expression profiles of miRNA and mRNA with the human PIN to reveal miRNA-regulated PIN in specific biological conditions. The potential functions of miRNAs were determined by functional enrichment analysis and the activities of miRNA-regulated PINs were evaluated by the co-expression of protein-protein interactions (PPIs). The function of a specific miRNA, miR-148a, was further examined by clinical data analysis and cell-based experiments. We uncovered several miRNA-regulated networks which were enriched with functions related to cancer progression. One miRNA, miR-148a, was identified and its function is to decrease tumor proliferation and metastasis through its regulated PIN. Furthermore, we found that miR-148a could reduce the invasiveness, migratory and adhesive activities of gastric tumor cells. Most importantly, elevated miR-148a level in gastric cancer tissues was strongly correlated with distant metastasis, organ and peritoneal invasion and reduced survival rate.ConclusionsThis study provides a novel method to identify active oncomirs and their potential functions in gastric cancer progression. The present data suggest that miR-148a could be a potential prognostic biomarker of gastric cancer and function as a tumor suppressor through repressing the activity of its regulated PIN.

Expression and clinical significance of the microRNA-200 family in gastric cancer

“…This is mainly a result of patients being diagnosed late and the consequently low surgical resection rate (1)(2)(3). An improved understanding of the pathogenesis and pathological characteristics of gastric cancer will provide a novel method to ensure an early diagnosis and treatment.…”

812 Comparison of Microarray Platforms for Measuring Differential MicroRNA Expression in Paired Normal/cancer Colon Tissues

“…Figure S1 Distribution of differential expression of miRNAs (log 2 fold changes) dependent on the origin of analyzed samples. Four publicly available datasets, obtained on Agilent platform were used for distribution comparison: GSE13860 and E-MTAB-96 datasets belonging to miRNA cross-platform comparison studies (Table S1); GSE21036 dataset, 28 paired primary prostate tumors and normal matched tissues profiled on Agilent v2.0 arrays, designed on miRBase release 10.1 [12]; GSE28700 dataset, 22 paired gastric cancers and normal matched tissues profiled on Agilent v1.0 arrays, designed on miRBase 10.1 [13]. (PDF) Figure S2 RLE plots.…”

Integrative network analysis of rifampin-regulated miRNAs and their functions in human hepatocytes

“…MiRNA can indirectly influence rifampin-induced drug deposition through gene regulation [11,[13][14][15]. Proteins are synthesized from mRNA templates through a highly conserved process, many studies have reported that the functions of miRNAs can be understood by analyzing miRNAs-regulated mRNA-related PIN [16][17][18].…”