Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A patient with liver cirrhosis who progressed to hepatocellular carcinoma was found to develop novel antinuclear antibodies. The serum was used to isolate full-length cDNA clones encoding related proteins of 530 amino acids (representative clone HCC1.4) and 524 amino acids (representative clone HCC1.3). Affinity-purified antibodies eluted from recombinant proteins recognized a 64-kD nuclear protein in Western blotting and decorated the nucleoplasm in a speckled-network fashion in immunofluorescence, colocalizing with antibodies to pre-mRNA splicing factor SC35 and uridine-rich small nuclear RNAs. The deduced amino acid sequence contained an arginine/serine-rich (RS) domain and three-ribonucleoprotein consensus sequence domains, two classes of motifs present in several splicing factors. A repeating octapeptide of Arg-Ser-Arg-Ser-Arg(Lys)-Glu(Asp)-Arg-Lys(Arg) was present in RS region of HCC1. This octapeptide sequence called RS-ERK motif was also found in splicing factors U2AF 35- and 65-kD proteins and 70-kD U1 small nuclear ribonucleoprotein. The molecular features and immunolocalization data suggest that the HCC1 autoantigen may be associated with splicing activities and are consistent with observations that autoantibody responses frequently target molecules involved in important cellular biosynthetic functions.
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PMID:Novel nuclear autoantigen with splicing factor motifs identified with antibody from hepatocellular carcinoma. 822 58

We describe the characterization of a gene, Pad-1, from Neurospora crassa which displays sequence characteristics of the RS class of hnRNA-binding proteins (hnRNP) and mRNA splicing factors. This is the first report of the isolation of a putative hnRNP gene from N. crassa. PAD-1 showed 30% identity and 57% similarity to a protein, HCC1, which was isolated using autoantibodies from patients suffering from hepatocellular carcinoma. Both HCC1 and PAD-1 show amino acid sequence similarities to the human splicing factor, U2AF65. Mutations induced in Pad-1 by repeat-induced point (RIP) mutation show dominant effects on ascus and ascospore formation, a novel phenotypic class of RIP mutants. A mutant isolated from the Pad-1 RIP cross displayed a severe vegetative growth defect and dominant effects on ascus development, indicating that Pad-1 is essential for both asexual and sexual development.
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PMID:Repeat-induced point mutations in Pad-1, a putative RNA splicing factor from Neurospora crassa, confer dominant lethal effects on ascus development. 957 30

Hepatocellular carcinoma (HCC) is one of the most prevalent cancers. It has been demonstrated that various cellular microRNAs (miRNAs) play an important role in HCC development. Here, we analyzed the miRNA profile in HCC tissues by Solexa sequencing, and we identified a novel microRNA, miR-HCC1, which is upregulated in HCC tissues. Further experiments showed that miR-HCC1 promoted HCC cell proliferation in vivo and in vitro, and migration and invasion resulting from the epithelial-mesenchymal transition (EMT) process. Nuclear factor I/X (NFIX), which inhibited cell proliferation, migration and invasion in HCC cells, was identified as a direct and functional target of miR-HCC1. Furthermore, lymphoid enhancer binding factor 1 (LEF1), a transcription factor, was shown to bind the promoter of miR-HCC1 and activate its expression. Collectively, these results indicate that LEF1-upregulated miR-HCC1 functions as an oncogene through the negative regulation of NFIX expression, which links the LEF1/miR-HCC1/NFIX axis to contribute to cell proliferation, migration and invasion of HCC cells and could provide novel insights into miRNA function and hepatocarcinogenesis and potential biomarkers for HCC.
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PMID:A novel microRNA identified in hepatocellular carcinomas is responsive to LEF1 and facilitates proliferation and epithelial-mesenchymal transition via targeting of NFIX. 2947 29