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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.
Highlights
MicroRNAs 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
The miRNA-regulated protein interaction network (PIN) were established according to the proteins encoded by differentially expressed target genes and their interacting partners in the human PIN
In order to reveal the possible roles that these miRNAs play in gastric cancer, the predicted target genes of miRNAs were analyzed within the human PIN and it was shown that a stronger functional correlation existed for miRNA targets that were linked to specific protein-protein interactions (PPIs) partners than for miRNA targets alone
Summary
MicroRNAs (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. The complementarity is between seed regions of mature miRNAs and their target messengers, enabling miRNA-mRNA interactions to occur. Li et al combined sequence complementarity, miRNA expression level, and protein abundance to identify miRNA targets for elevating their predictions. They found that translational repression of targets by miRNAs was dominant mechanism in miRNA regulation. The development of an integrative approach that incorporated expression data to facilitate the identification of condition-specific targets of miRNAs becomes increasingly important
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