Integrative network analysis reveals active microRNAs and their functions in gastric cancer
- Equal contributors
1 Institute of Molecular and Cellular Biology and Department of Life Science, National Taiwan University, Taipei 106, Taiwan
2 Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei 106, Taiwan
3 Institute of Biomedical Informatics and Center for Systems and Synthetic Biology, National Yang-Ming University, Taipei 112, Taiwan
4 Angiogenesis Research Center, National Taiwan University, Taipei 106, Taiwan
5 Department of Surgery, National Taiwan University Hospital and College of Medicine, Taipei 100, Taiwan
BMC Systems Biology 2011, 5:99 doi:10.1186/1752-0509-5-99Published: 26 June 2011
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. 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.
We 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.
This 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.