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Elevated expression of A-Raf and FA2H in hepatocellular carcinoma is associated with lipid metabolism dysregulation and cancer progression.

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Identification of events leading to HCC progression is essential for understanding its pathophysiology. Present study was designed to identify differentially expressed proteins in serum of HCC-bearing rats vis-a-vis controls during… Click to show full abstract

Identification of events leading to HCC progression is essential for understanding its pathophysiology. Present study was designed to identify differentially expressed proteins in serum of HCC-bearing rats vis-a-vis controls during cancer initiation, progression and tumorigenesis. HCC was chemically induced by administering N-Nitrosodiethylamine and 2-aminoacetylfluorine to male Wistar rats. Carcinogen administration caused inflammation leading to liver injury and HCC development. Liver inflammation was confirmed by increase in levels of IL-6 and TNF-α in carcinogen treated rats. The 2D-Gel Electrophoresis and MALD-TOF-MS analysis identified several differentially expressed proteins in serum of HCC-bearing animals vis-a-vis age-matched controls. We report significant elevation in expression of two of these proteins, namely, A-Raf and fatty acid 2-hydroxylase (FA2H), at early stage of HCC initiation, during its progression and at tumor stage. The elevated-expression was validated by Western blot analysis. Real-time PCR analysis of mRNA isolated from tumor tissues confirmed up-regulation of their transcripts. Further, we validated our experimental data in serum of clinically confirmed liver cancer patients. Furthermore, we have identified a novel HCC-specific network among these proteins and their interactors representing a complex inter-relationship between signaling pathways that may regulate HCC development. The study suggests that FA2H and A-Raf play major role in HCC progression .

Keywords: hcc; expression raf; cancer; progression; elevated expression

Journal Title: Anti-cancer agents in medicinal chemistry
Year Published: 2018

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