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Identification of Biomarker and Co-Regulatory Motifs in Lung Adenocarcinoma Based on Differential Interactions.

Zhao N, Liu Y, Chang Z, Li K, Zhang R, Zhou Y, Qiu F, Han X, Xu Y - PLoS ONE (2015)

Bottom Line: Moreover, several biological functions (i.e., cell cycle, signaling pathways and hemopoiesis) associated with the three motifs were found to be frequently targeted by the drugs for lung adenocarcinoma.A 10-gene biomarker (UBC, SRC, SP1, MYC, STAT3, JUN, NR3C1, RB1, GRB2 and MAPK1) was selected from the joint motif, and a survival analysis indicated its significant association with survival.The genes, regulators and regulatory motifs detected in this work will provide potential drug targets and new strategies for individual therapy.

View Article: PubMed Central - PubMed

Affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China.

ABSTRACT
Changes in intermolecular interactions (differential interactions) may influence the progression of cancer. Specific genes and their regulatory networks may be more closely associated with cancer when taking their transcriptional and post-transcriptional levels and dynamic and static interactions into account simultaneously. In this paper, a differential interaction analysis was performed to detect lung adenocarcinoma-related genes. Furthermore, a miRNA-TF (transcription factor) synergistic regulation network was constructed to identify three kinds of co-regulated motifs, namely, triplet, crosstalk and joint. Not only were the known cancer-related miRNAs and TFs (let-7, miR-15a, miR-17, TP53, ETS1, and so on) were detected in the motifs, but also the miR-15, let-7 and miR-17 families showed a tendency to regulate the triplet, crosstalk and joint motifs, respectively. Moreover, several biological functions (i.e., cell cycle, signaling pathways and hemopoiesis) associated with the three motifs were found to be frequently targeted by the drugs for lung adenocarcinoma. Specifically, the two 4-node motifs (crosstalk and joint) based on co-expression and interaction had a closer relationship to lung adenocarcinoma, and so further research was performed on them. A 10-gene biomarker (UBC, SRC, SP1, MYC, STAT3, JUN, NR3C1, RB1, GRB2 and MAPK1) was selected from the joint motif, and a survival analysis indicated its significant association with survival. Among the ten genes, JUN, NR3C1 and GRB2 are our newly detected candidate lung adenocarcinoma-related genes. The genes, regulators and regulatory motifs detected in this work will provide potential drug targets and new strategies for individual therapy.

No MeSH data available.


Related in: MedlinePlus

The boxplot of expressed comparison of the top ten genes in Joint.For each gene, the left box is the expression of control samples and the right box is the expression of disease samples. Only JUN and NR3C1 are differentially expressed between disease and control samples.
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pone.0139165.g004: The boxplot of expressed comparison of the top ten genes in Joint.For each gene, the left box is the expression of control samples and the right box is the expression of disease samples. Only JUN and NR3C1 are differentially expressed between disease and control samples.

Mentions: Among these ten genes, only JUN and NR3C1 were identified as being differentially expressed genes (Fig 4). They are all lung adenocarcinoma-related genes specifically detected by differential interactions. This further verified the robustness of our approach. JUN and NR3C1 were detected by both differential interactions and by differential expression, increasing their possibility to be correlated with lung adenocarcinoma.


Identification of Biomarker and Co-Regulatory Motifs in Lung Adenocarcinoma Based on Differential Interactions.

Zhao N, Liu Y, Chang Z, Li K, Zhang R, Zhou Y, Qiu F, Han X, Xu Y - PLoS ONE (2015)

The boxplot of expressed comparison of the top ten genes in Joint.For each gene, the left box is the expression of control samples and the right box is the expression of disease samples. Only JUN and NR3C1 are differentially expressed between disease and control samples.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4581687&req=5

pone.0139165.g004: The boxplot of expressed comparison of the top ten genes in Joint.For each gene, the left box is the expression of control samples and the right box is the expression of disease samples. Only JUN and NR3C1 are differentially expressed between disease and control samples.
Mentions: Among these ten genes, only JUN and NR3C1 were identified as being differentially expressed genes (Fig 4). They are all lung adenocarcinoma-related genes specifically detected by differential interactions. This further verified the robustness of our approach. JUN and NR3C1 were detected by both differential interactions and by differential expression, increasing their possibility to be correlated with lung adenocarcinoma.

Bottom Line: Moreover, several biological functions (i.e., cell cycle, signaling pathways and hemopoiesis) associated with the three motifs were found to be frequently targeted by the drugs for lung adenocarcinoma.A 10-gene biomarker (UBC, SRC, SP1, MYC, STAT3, JUN, NR3C1, RB1, GRB2 and MAPK1) was selected from the joint motif, and a survival analysis indicated its significant association with survival.The genes, regulators and regulatory motifs detected in this work will provide potential drug targets and new strategies for individual therapy.

View Article: PubMed Central - PubMed

Affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China.

ABSTRACT
Changes in intermolecular interactions (differential interactions) may influence the progression of cancer. Specific genes and their regulatory networks may be more closely associated with cancer when taking their transcriptional and post-transcriptional levels and dynamic and static interactions into account simultaneously. In this paper, a differential interaction analysis was performed to detect lung adenocarcinoma-related genes. Furthermore, a miRNA-TF (transcription factor) synergistic regulation network was constructed to identify three kinds of co-regulated motifs, namely, triplet, crosstalk and joint. Not only were the known cancer-related miRNAs and TFs (let-7, miR-15a, miR-17, TP53, ETS1, and so on) were detected in the motifs, but also the miR-15, let-7 and miR-17 families showed a tendency to regulate the triplet, crosstalk and joint motifs, respectively. Moreover, several biological functions (i.e., cell cycle, signaling pathways and hemopoiesis) associated with the three motifs were found to be frequently targeted by the drugs for lung adenocarcinoma. Specifically, the two 4-node motifs (crosstalk and joint) based on co-expression and interaction had a closer relationship to lung adenocarcinoma, and so further research was performed on them. A 10-gene biomarker (UBC, SRC, SP1, MYC, STAT3, JUN, NR3C1, RB1, GRB2 and MAPK1) was selected from the joint motif, and a survival analysis indicated its significant association with survival. Among the ten genes, JUN, NR3C1 and GRB2 are our newly detected candidate lung adenocarcinoma-related genes. The genes, regulators and regulatory motifs detected in this work will provide potential drug targets and new strategies for individual therapy.

No MeSH data available.


Related in: MedlinePlus