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

Tseng CW, Lin CC, Chen CN, Huang HC, Juan HF - BMC Syst Biol (2011)

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Molecular and Cellular Biology and Department of Life Science, National Taiwan University, Taipei 106, Taiwan.

ABSTRACT

Background: 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.

Results: 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.

Conclusions: 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.

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Expression profiles of miRNAs and genes were used to discover condition-specific targets of miRNAs. The miRNA-regulated PINs were denoted as the PIN which is formed by their differentially expressed targets (L0) and interacting partners (L1). The enrichment of CePPIs involved in the miRNA-regulated PIN was utilized to evaluate the activity of the network. The potential miRNA-regulated functions were predicted by functional enrichment analysis.
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Figure 1: Expression profiles of miRNAs and genes were used to discover condition-specific targets of miRNAs. The miRNA-regulated PINs were denoted as the PIN which is formed by their differentially expressed targets (L0) and interacting partners (L1). The enrichment of CePPIs involved in the miRNA-regulated PIN was utilized to evaluate the activity of the network. The potential miRNA-regulated functions were predicted by functional enrichment analysis.

Mentions: In this study, we proposed an integrative analysis which suggested that miRNA-regulated PINs could be identified based on the combination of down-regulated miRNAs and up-regulated mRNAs. The procedure for miRNA-regulated PIN identification and analysis is illustrated in Figure 1. We subsequently showed that the networks that were modulated by these down-regulated miRNAs in tumors tended to be activated in gastric cancer. Among these was the miR-148a-regulated PIN, which was involved in metastasis-related biological processes that were associated with tumor suppression. In particular, miR-148a was shown to inhibit tumor invasion, migration, adhesion and cell growth, and prolonged patient survival. These findings suggest that miR-148a is not only a potential prognostic marker that can be used for the detection of human gastric cancer, but it can also suppress gastric cancer progression through the regulation of its associated network.


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

Tseng CW, Lin CC, Chen CN, Huang HC, Juan HF - BMC Syst Biol (2011)

Expression profiles of miRNAs and genes were used to discover condition-specific targets of miRNAs. The miRNA-regulated PINs were denoted as the PIN which is formed by their differentially expressed targets (L0) and interacting partners (L1). The enrichment of CePPIs involved in the miRNA-regulated PIN was utilized to evaluate the activity of the network. The potential miRNA-regulated functions were predicted by functional enrichment analysis.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3142228&req=5

Figure 1: Expression profiles of miRNAs and genes were used to discover condition-specific targets of miRNAs. The miRNA-regulated PINs were denoted as the PIN which is formed by their differentially expressed targets (L0) and interacting partners (L1). The enrichment of CePPIs involved in the miRNA-regulated PIN was utilized to evaluate the activity of the network. The potential miRNA-regulated functions were predicted by functional enrichment analysis.
Mentions: In this study, we proposed an integrative analysis which suggested that miRNA-regulated PINs could be identified based on the combination of down-regulated miRNAs and up-regulated mRNAs. The procedure for miRNA-regulated PIN identification and analysis is illustrated in Figure 1. We subsequently showed that the networks that were modulated by these down-regulated miRNAs in tumors tended to be activated in gastric cancer. Among these was the miR-148a-regulated PIN, which was involved in metastasis-related biological processes that were associated with tumor suppression. In particular, miR-148a was shown to inhibit tumor invasion, migration, adhesion and cell growth, and prolonged patient survival. These findings suggest that miR-148a is not only a potential prognostic marker that can be used for the detection of human gastric cancer, but it can also suppress gastric cancer progression through the regulation of its associated network.

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Molecular and Cellular Biology and Department of Life Science, National Taiwan University, Taipei 106, Taiwan.

ABSTRACT

Background: 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.

Results: 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.

Conclusions: 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.

Show MeSH
Related in: MedlinePlus