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dc.coverage.spatialBelo Horizontees_CL
dc.creatorMarquez-Montecinos, José Carlos
dc.creatorSarmiento-Godoy, Sebastián
dc.creatorChacon, Carlos
dc.creatorUrzua-Tobar, Ulises De La Cruz
dc.description.abstractBackground: Ovarian cancer (OC) continues to be the top ranking deadliest gynecological cancer worldwide. Several epidemiologic studies have shown an inverse relationship between OC risk and parity. Compared to the nulliparous state, pregnancy leads to altered levels in over a dozen of peptide and steroid hormones, which might imprint a long term protective effect against OC. Based in previous studies of parity genes in the mouse ovary and the human breast, here we show in silico evidence of pathways, networks, transcriptional and post-transcriptional control mechanisms presumably involved in the protective effect of parity against OC. Results: Fifty-three genes were coincident between a parous ovary (PO) associated gene set with a cancer related (CA) gene set retrieved from 14 cancer genes databases and querying tools. Six of these 53 PO-CA genes (RHOA, PTEN, DMTF1, DDX3X, IRF3, SALL4 and RBM6) have been cataloged as tumor suppressor genes in TSGene and 3 (XRCC3, CLK2 and FANCM) as DNA repair genes in REPAIRtoire. Importantly, HNRNPA2B1, CCNL1, OGT, FUBP1, LUC7L3, MALAT1, RBM25 and HNRPDL were also found in a human parous breast list. The PO-CA genes were subjected to GO, KEGG and WikiPathways analysis with WebGestalt. Recurrent enriched functions (P<0.05) in the 38 PO-CA up-regulated genes were decoded as hypernyms terms including RNA/mRNA processing and nuclear export, DNA damage/cell death response, post-translational histone modification, and nuclear speckles/bodies. PTEN, RHOA, HNRNPA2B1, RBM25, SRSF2, DDX3X, NXF1 and SON were recurrent in at least 4 functional terms. On the other hand, transcription factors LEF1, SP1, MAZ and YY1 and micro-RNAs MIR-193A, MIR-361 and MIR-15A were the most recurrent molecules that might exert transcriptional and post-transcriptional control of PO-CA genes expression. Based on a MCL algorithm, 7 clusters were identified in a gene interaction network using STRING v9.2. In a central 11-member cluster, 6 genes showed MAZ and 5 genes showed LEF1 binding sites, with 3 genes overlapping both transcription factors. The same cluster contained 5 genes sharing the RNA recognition motif domain. Conclusion: Enriched functions of PO-CA genes resembles parous breast with an overlap of 8 genes suggesting a common protective mechanism governed by pregnancy hormones. Nearly 1/5 of PO-CA genes are linked to tumor suppression and DNA repair. Our analysis supports the idea that the robustness of both the splicing machinery and the nuclear export mechanism ensures genome stability. Similarly, nuclear localization of tumor suppressor PTEN has been described to require integrity of nuclear bodies. Finally, up-regulation of post-translational histone modification genes would be essential to preserve the OC protective signature.es_CL
dc.relationinstname: Conicyt
dc.relationreponame: Repositorio Digital RI2.0
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 Chile*
dc.titleA genomic aproach to the molecular basis of the effect of parity on ovarian cancer riskes_CL
dc.relation.namecongISCB-Latin America Meeting on Bioinformatics with BSB & SoiBioes_CL

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