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Chronic Liver Diseases Which Mallory‐Denk Body (MDB) Form Progress to Hepatocellular Carcinoma is Involved in Ufmylation and FATylation Modification (LB493)
Author(s) -
Liu Hui,
Li Jun,
French Barbara A,
French Samuel W
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.lb493
Subject(s) - hepatocellular carcinoma , downregulation and upregulation , chronic liver disease , liver biopsy , liver disease , liver cancer , cancer research , biopsy , medicine , gene , biology , pathology , biochemistry , cirrhosis
We previously reported the Mallory‐Denk body (MDB) formation mechanism in DDC induced mice. To further provide clinical evidence whether chronic liver diseases which MDB form progress to hepatocellular carcinoma (HCC) is involved in Ubiquitin‐like proteins (Ubls) modification, gene transcript expression of Ufmylation and FATylation were investigated in human archived formalin‐fixed, paraffin‐embedded (FFPE) liver biopsy and mice frozen liver section from DDC refeding. It showed that all Ufmylation molecules (Ufm1, Uba5, Ufc1, Ufl1 and UfSPs) were at least 50% down regulated both in DDC refed mice and patient liver except for HCC without MDB biopsy, indicating that gene transcript changes was limited in MDB‐forming cells for a signal of proteasomal degredation. Interestedly, FAT10 and subunits of the immunoproteasome (LMP2, LMP7 and MECL‐1) were all up regulated. Among which, a 45‐ and 7‐fold upregulation of FAT10 were observed in DDC refed mice liver and human alcoholic hepatitis with MDB biopsy respectively, implying an important role of this gene. The FAT10‐specific E1 enzyme UBA6, however, was found to down regulation both in patient and DDC refed mice liver. Our results constitute the first systematic demonstration of transcript regulation of Ufmylation and FATylation in liver patient which MDB form progress to HCC and mice MDB‐forming liver by DDC refeding, providing key clue for the investigation of human liver disease development and strategies for drug design. Grant Funding Source : Supported by NIH(RO1 AA021898‐02)