title: Inhibitory effect of alternatively spliced  RAGEv1 on the expression of NF-kB and TNF-α in hepatocellular carcinoma cells.
abstract: Binding of specific ligands to the receptor for  advanced glycation end-products (RAGE) can trigger a series of signal  transductions, which leads to pathogenesis in many chronic degenerative  diseases, including cancer. Alternative splicing of RAGE mRNA has resulted in  many variants, including RAGE variant 1 (RAGEv1). This particular splice  variant of RAGE can provide a major soluble form of RAGE in blood circulation,  which can neutralize deleterious ligands, thus diminishing signaling that can  lead to inflammation and pathogenesis in cancer cells. However, the molecular  mechanisms involved in suppressing signaling cascades in the cells are unknown.  We investigated the molecular role of the RAGEv1 isoform in modulating NF-kB  and TNF-α gene  expression in human hepatocellular carcinoma HepG2 cells. Transient  transfection using an engineered plasmid containing the RAGEv1 gene resulted in  a significant increase in normalized RAGEv1 mRNA transcripts in HepG2 cells.  This finding was supported by the detection of the RAGEv1 protein, which was  found in the whole-cell extracts and the cell culture media. This high degree  of RAGEv1 expression significantly reduced the expression of normalized mRNA  transcripts of NF-kB and TNF-α in HepG2 cells. We suggest that RAGEv1 could reduce  activity of the NF-kB signaling pathway in liver cancer cells, thus providing a  potential alternative therapy for the treatment of liver cancer.
authors: Graduate Program in Clinical Biochemistry and Molecular Medicine, Department of Clinical Chemistry, Faculty of Allied Health Sciences, Chulalongkorn University, Bangkok, Thailand.
authors: T
authors: T
authors: Lertwittayapon
authors: T
authors: T
authors: Tencomnao
authors: R
authors: R
authors: Santiyanont
mesh_terms: D017398:Alternative Splicing; D006528:Carcinoma, Hepatocellular; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D000067759:Receptor for Advanced Glycation End Products / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
chemical_list: D007527:Isoenzymes; D016328:NF-kappa B; D000067759:Receptor for Advanced Glycation End Products; D014409:Tumor Necrosis Factor-alpha