Sense-antisense gene-pairs in breast cancer and associated pathological pathways

作者: Oleg V. Grinchuk , Efthymios Motakis , Surya Pavan Yenamandra , Ghim Siong Ow , Piroon Jenjaroenpun

DOI: 10.18632/ONCOTARGET.6255

关键词:

摘要: More than 30% of human protein-coding genes form hereditary complex genome architectures composed sense-antisense (SA) gene pairs (SAGPs) transcribing their RNAs from both strands a given locus. Such represent important novel components complexity contributing to expression deregulation in cancer cells. Therefore, the might be involved pathways and, turn, used for drug targets discovery. However, global roles SAGPs has not been studied. Here we investigated associated with breast (BC)-related using systems biology, prognostic survival and experimental methods. Gene analysis identified 73 BC-relevant that are highly correlated BC. Survival modelling metadata 1161 BC patients allowed us develop patient grouping method selecting 12 survival-significant SAGPs. The qRT-PCR-validated 12-SAGP signature reproducibly stratified into low- high-risk subgroups. 1381 SAGP-defined differentially expressed common across three studied cohorts were identified. functional enrichment these revealed GABPA network, including SAGPs, specific sets cell cycle, spliceosomal proteasomal pathways. co-regulatory function cells was supported siRNA knockdown studies. Thus, demonstrated as synergistically interconnected cancer-related clinical outcomes. Taken together, an component which can identify aspects coordinated pathological networks cancers.

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