Identification of -driven gene signatures and key signaling networks in ovarian cancer.

With the focus on defining the oncogenic network stimulated by lysophosphatidic acid (LPA) in ovarian cancer, the present study sought to interrogate the oncotranscriptome regulated by the LPA-mediated signaling pathway. LPA, LPA-receptor (LPAR) and LPAR-activated G protein 12 α-subunit, encoded by G protein subunit α 12 (), all serve an important role in ovarian cancer progression. While the general signaling mechanism regulated by LPA/LPAR/ has previously been characterized, the global transcriptomic network regulated by in ovarian cancer pathophysiology remains largely unknown. To define the LPA/LPAR/-orchestrated oncogenic networks in ovarian cancer, transcriptomic and bioinformatical analyses were conducted using SKOV3 cells, in which the expression of was silenced. Array analysis was performed in Agilent SurePrint G3 Human Comparative Genomic Hybridization 8×60 microarray platform. The array results were validated using Kuramochi cells. Gene and functional enrichment analyses were performed using Database for Annotation, Visualization and Integrated Discovery, Search Tool for Retrieval of Interacting Genes and Cytoscape algorithms. The results indicated a paradigm in which drove ovarian cancer progression by upregulating a pro-tumorigenic network with , insulin-like growth factor 1 and growth hormone releasing hormone as critical hub and/or bottleneck nodes. Moreover, downregulated a growth-suppressive network involving proteasome 20S subunit (PSM) β6, α6, ATPase 5, ubiquitin conjugating enzyme E2 E1, non-ATPase 10, NDUFA4 mitochondrial complex-associated, NADH:ubiquinone oxidoreductase subunit B8 and anaphase promoting complex subunit 1 as hub or bottleneck nodes. In addition to providing novel insights into the LPA/LPAR/-regulated oncogenic networks in ovarian cancer, the present study identified several potential nodes in this network that could be assessed for targeted therapy.