Basic–liver, pancreas, and biliary tractCharacterization of HULC, a Novel Gene With Striking Up-Regulation in Hepatocellular Carcinoma, as Noncoding RNA
Section snippets
Human Tissues
Human tissue samples were retrieved from the biobank at the Institute of Pathology, Medical University of Graz, Austria. Tissues obtained from surgically resected tumors and adjacent non-neoplastic tissue or from explanted livers were either snap frozen in methyl butane precooled with liquid nitrogen within 20 minutes after operation or fixed in phosphate-buffered (pH 7.4) 4% formaldehyde solution and embedded in paraffin. The study was approved by the ethics committee of the Medical University
HULC Is Specifically Expressed in Hepatocytes and Highly Up-regulated in HCC
For a genome-wide gene expression profiling approach, we generated HCC-specific cDNA libraries by subtractive suppressive hybridization.21 Clones from the HCC cDNA library in conjunction with well-known cancer-related and control genes were used for the production of an HCC-specific cDNA microarray containing a total of 6912 cDNA clones. Tissue samples of 46 HCCs, 4 FNHs, 7 cirrhoses, and 2 non-neoplastic livers were compared with a pool of non-neoplastic liver samples (Figure 1A; full dataset
Discussion
Using an HCC-specific cDNA microarray platform, we identified HULC, a novel mRNA-like ncRNA, as 1 of the most up-regulated genes in HCC. The levels of HULC RNA expression and up-regulation exceeded well-established, cancer-related genes analyzed in our study as well as those identified in other gene expression profiling studies.30, 31, 32 Examples of such genes are the E2F targets proliferating cell nuclear antigen and histone 1, the proliferation-associated genes cyclin D1, and c-jun, the
References (41)
Non-coding RNAs: new players in eukaryotic biology
Gene
(2005)- et al.
JAZF1/JJAZ1 gene fusion in endometrial stroma sarcomas
J Mol Diagn
(2005) - et al.
Cytokeratins as targets for bile acid-induced toxicity
Am J Pathol
(2002) - et al.
Overexpression of glutamine synthetase in human primary liver cancer
Gastroenterology
(1994) - et al.
The fragile X syndrome protein FMRP associates with BC1 RNA and regulates the translation of specific mRNAs at synapses
Cell
(2003) - et al.
Liver tumor developmentc-Jun antagonizes the proapoptotic activity of p53
Cell
(2003) - et al.
A Dicer-2-dependent 80s complex cleaves targeted mRNAs during RNAi in Drosophila
Cell
(2004) Non-coding RNAs: the architects of eukaryotic complexity
EMBO Rep
(2001)- et al.
MicroRNA expression profiles classify human cancers
Nature
(2005) - et al.
Identification of hundreds of conserved and nonconserved human microRNAs
Nat Genet
(2005)
Modulation of hepatitis C virus RNA abundance by a liver-specific microRNA
Science
Collection of mRNA-like non-coding RNAs
Nucleic Acids Res
Bic, a novel gene activated by proviral insertions in avian leukosis virus-induced lymphomas, is likely to function through its non-coding RNA
Mol Cell Biol
MALAT-1, a novel non-coding RNA, and thymosin beta4 predict metastasis and survival in early-stage non-small cell lung cancer
Oncogene
Expression of neural BC200 RNA in human tumours
J Pathol
Expression of the putative proto-oncogene His-1 in normal and neoplastic tissues
Am J Pathol
PCGEM1, a prostate-specific gene, is overexpressed in prostate cancer
Proc Natl Acad Sci U S A
DD3: a new prostate-specific gene, highly overexpressed in prostate cancer
Cancer Res
Elevated expression of PCGEM1, a prostate-specific gene with cell growth-promoting function, is associated with high-risk prostate cancer patients
Oncogene
BC200 RNA in invasive and preinvasive breast cancer
Carcinogenesis
Cited by (0)
Supported by the Austrian Science Fund (FWF) grant #S7401-MOB, the Austrian Industrial Research Promotion Fund (FFF) grant #804714, the Austrian Genome Program GEN-AU, and the Lore Saldow Fund.
- 1
K.P. and M.M.O.T. contributed equally to this work.
- 2
Current address for Christian Guelly, Tarek, Moustafa, Martin Stradner, and Heimo M. Strohmaier: Center for Medical Research, Medical University of Graz, Stiftingtalstrasse 24, 8010 Graz, Austria.
- 3
Current address for Charles R. Buck: Bindley Bioscience Center, Purdue University, West Lafayette, IN 47907.