title: Identification of Biomarker and Co-Regulatory Motifs in Lung Adenocarcinoma Based on Differential Interactions.
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.
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhao
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China.
authors.forename: Yongjing
authors.initials: Y
authors.lastname: Liu
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Chang
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China.
authors.forename: Kening
authors.initials: K
authors.lastname: Li
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China.
authors.forename: Yuanshuai
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China.
authors.forename: Fujun
authors.initials: F
authors.lastname: Qiu
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China.
authors.forename: Xiaole
authors.initials: X
authors.lastname: Han
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, 150081, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D000077192:Adenocarcinoma of Lung; D014408:Biomarkers, Tumor / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D063990:Gene Ontology; D053263:Gene Regulatory Networks; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; D014157:Transcription Factors