Genome-wide expression analysis of cells expressing gain of function mutant D374Y-PCSK9.
作者： Trine Ranheim , Morten Mattingsdal , Jessica M. Lindvall , Øystein L. Holla , Knut Erik Berge
DOI: 10.1002/JCP.21519
关键词:
摘要: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulator of serum cholesterol. The possibility that PCSK9 also functions in other pathways needs to be addressed. We have transfected HepG2 cells with mutant D374Y-PCSK9 or control vector. Gene expression signatures were determined using the Affymetrix GeneChip technology, and pattern selected genes was confirmed by quantitative real-time polymerase chain reaction (qRT-PCR). Data normalized analyzed model-based background adjustment for oligonucleotide arrays, then filtered based upon within treatments group, subjected moderated t-statistics. Five hundred twenty transcripts had altered levels between Among 520 probes on our top list, 312 found an assigned Ontology (GO) term, 96 Kyoto Encyclopedia Genes Genomes (KEGG) pathways. Genome-wide profiling revealed "steroid biosynthesis," "sterol metabolism," "cholesterol biosynthsis" affected D374Y-PCSK9. Also, GO biological process terms "response stresss," virus," unfolded protein," "immune response" influenced Our results suggest up-regulation involved sterol biosynthesis down-regulation stress-response specific inflammation
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