Difference between revisions of "NONHSAT107640"

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Please input one-sentence summary here.
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''HULC'' : Highly upregulated in liver cancer RNA is characterized as a novel mRNA-like ncRNA which is associated with cancer progression. <ref name="ref1" />
  
 
==Annotated Information==
 
==Annotated Information==
 
===Name===
 
===Name===
HULC: Highly upregulated in liver cancer RNA
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HULC: hepatocellular carcinoma up-regulated long non-coding RNA [https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:34232 (HGNC:34232)]
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===Aliases===
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NCRNA00078: non-protein coding RNA 78, LINC00078: long intergenic non-protein coding RNA 78, HCCAT1: hepatocellular carcinoma associated transcript 1 (non-protein coding) [https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:34232 (HGNC:34232)]
  
 
===Characteristics===
 
===Characteristics===
~500nuc, spliced, polyadenylated, two exon transcript [http://www.ncbi.nlm.nih.gov/pubmed/17241883 (Panzitt (2007))]. Exon 1 mainly consists of an LTR (MLT1A) [http://www.ncbi.nlm.nih.gov/pubmed/17241883 (Panzitt (2007))].
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''HULC'' RNA is ~500nuc, spliced and polyadenlyated,localized on human chromosome 6p24.3 and resembles the mammalian LTR transposon 1A. One striking feature of the ''HULC'' RNA sequence is the high density of stop codons in the small potential reading frames scattered throughout the ''HULC'' gene. It does not contain substantial open reading frames, and no protein product was detected. ''HULC'' is present in the cytoplasm, where it copurifies with ribosomes. The ''HULC'' gene includes a single intron and carries 1 canonical and 2 noncanonical polyadenylation signals 21 nt, 32 nt, and 47 nt, respectively, upstream from the polyA tail <ref name="ref1" />
  
 
===Function===
 
===Function===
Competing endogenous RNA (ceRNA). Functions as a sponge/ target mimic for miR-372 through a conserved target site, reducing the expression and activity of miR-372 [http://www.ncbi.nlm.nih.gov/pubmed/20423907 (Wang (2010))]. One of targets of miR-372 is Prkacb (catalytic subunit of PKA) which is able to phophorylate CREB. Hence expression of HULC stimulates further HULC expression by inhibiting miR-372, and allowing PRKACB to create active CREB [http://www.ncbi.nlm.nih.gov/pubmed/20423907 (Wang (2010))]. HULC knockdown affects expression of other genes including some described in liver cancer [http://www.ncbi.nlm.nih.gov/pubmed/17241883 (Panzitt (2007))].
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''HULC'' has a role in post-transcriptional modulation of gene expression. First clues about the function of ''HULC'' were obtained from siRNA-mediated knockdown of ''HULC'' in Hep3B and HepG2 cells, which resulted in a significant up- and down-regulation of several genes. <ref name="ref1" />
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''HULC'' may act as an endogenous ‘sponge’, which down-regulates a series of microRNAs (miRNAs) activities, including miR-372. Inhibition of miR-372 leads to reducing translational repression of its target gene, ''PRKACB'', which in turn induces phosphorylation of ''CREB''. <ref name="ref2" />
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===Regulation===
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PKA pathway may involved in up-regulation of HULC. <ref name="ref2" />
  
 
===Expression===
 
===Expression===
Binding of phospho-CREB to the HULC promoter activates HULC expression. Phosphorylation of CREB was stimulated by PKA signaling [http://www.ncbi.nlm.nih.gov/pubmed/20423907 (Wang (2010))]. Highly up-regulated in hepatocellular carcinoma (HCC) and to a lesser extent in liver focal nodular hyperplasia (FNH). Up-regulation was specific to HCC with high expression not detected in normal liver, other tissues and their associated neoplasms [http://www.ncbi.nlm.nih.gov/pubmed/17241883 (Panzitt (2007))]. HULC expression was also up-regulated in colorectal carcinomas that metastasised to the liver but not in primary colorectal carcinomas or carcinomas that metastasised to lymph nodes [http://www.ncbi.nlm.nih.gov/pubmed/19445043 (Matouk (2009))]. HULC RNA could be detected in the blood of HCC patients [http://www.ncbi.nlm.nih.gov/pubmed/17241883 (Panzitt (2007))]. Localised to the cytoplasm, may associate with ribosomes, but no sign of translated products could be found [http://www.ncbi.nlm.nih.gov/pubmed/17241883 (Panzitt (2007))]. HULC expression was also identified in 3 old world monkeys [http://www.ncbi.nlm.nih.gov/pubmed/17241883 (Panzitt (2007))].
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''HULC'' Is specifically expressed in Hepatocytes and highly up-regulated in HCC. ''HULC'' is the first ncRNA with highly specific up-regulation in HCC. It was detected in blood of HCC patients therefore can be used as a potential  biomarker. In contrast to the liver tumors, ''HULC'' is only slightly up-regulated in cirrhotic liver tissue and only barely detectable in most of the normal tissues. In situ hybridization revealed the specific and strong expression of ''HULC'' RNA in the cytoplasm of HCC, whereas it was not detected in tumor stroma and non-neoplastic liver cells. <ref name="ref1" />
  
===Conservation===
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''HULC'' was overexpressed in colorectal carcinomas that metastasize to the liver indicating that ''HULC'' expression is not confined to HCC. <ref name="ref3" />
HLUC also present in other primates, gene shows good conservation above that of surrounding sequence. Not detected in rodents so may be primate specific [http://www.ncbi.nlm.nih.gov/pubmed/17241883 (Panzitt (2007))].
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{| class='wikitable' style="text-align:center"
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|-
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! | Experiment
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! | Forward primer
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! | Reverse primer
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|-
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| rowspan="1"|Quantiative RT-PCR
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| | 5'-atctgcaagccaggaagagtc- 3'
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| | 5'-cttgcttgatgctttggtctgt- 3'<ref name="ref1" />
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|}
  
===Misc===
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===Diseases===
Please input misc information here.
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* Colorectal Carcinomas <ref name="ref3" />
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* Hepatocellular Carcinoma <ref name="ref1" />
  
===Transcriptomic Nomeclature===
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===Conservation===
Please input transcriptomic nomeclature information here.
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''HLUC'' also present in other primates, gene shows good conservation above that of surrounding sequence. Not detected in rodents so may be primate specific <ref name="ref1" />
  
===Regulation===
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==Labs working on this lncRNA==
PKA pathway may involved in up-regulation of HULC.
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* Institute of Pathology, Medical University of Graz, Graz, Austria
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* Oridis-Biomed, Graz, Austria
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* Max F. Perutz Laboratories, Vienna, Austria
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* Laboratory of Experimental and Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
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* Department of Biology, Science and Technology, Alquds Abu-Dis University, Jerusalem, Israel.
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* Department of Laboratory Medicine, Ruijin Hospital, Faculty of Medical Laboratory Science, Department of Pathology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025
  
===Allelic Information and Variation===
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==References==
Please input allelic information and variation information here.
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<references>
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<ref name="ref1"> Panzitt K, Tschernatsch MMO, Guelly C, Moustafa T, Stradner M, Strohmaier HM et al. Characterization of HULC, a Novel Gene With Striking Up-Regulation in Hepatocellular Carcinoma, as Noncoding RNA[J]. Gastroenterology. 2007, 132(1):330-342.</ref>(1)
  
===Evolution===
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<ref name="ref2"> Wang J, Liu X, Wu H, Ni P, Gu Z, Qiao Y et al. CREB up-regulates long non-coding RNA, HULC expression through interaction with microRNA-372 in liver cancer[J]. Nucleic acids research. 2010, 38(16):5366-5383.</ref>(2)
Please input evolution information here.
 
  
You can also add sub-section(s) at will.
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<ref name="ref3"> Matouk IJ, Abbasi I, Hochberg A, Galun E, Dweik H & Akkawi M. Highly upregulated in liver cancer noncoding RNA is overexpressed in hepatic colorectal metastasis[J]. European Journal of gastroenterology & hepatology. 2009, 21(6):688-692.</ref>(3)
 
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</references>
==Labs working on this lncRNA==
 
Please input related labs here.
 
 
 
==References==
 
[http://www.lncrnadb.org/HULC/ Annotation originally sourced from lncRNAdb.]
 
  
 
{{basic|
 
{{basic|

Revision as of 09:46, 22 November 2018

HULC : Highly upregulated in liver cancer RNA is characterized as a novel mRNA-like ncRNA which is associated with cancer progression. [1]

Annotated Information

Name

HULC: hepatocellular carcinoma up-regulated long non-coding RNA (HGNC:34232)

Aliases

NCRNA00078: non-protein coding RNA 78, LINC00078: long intergenic non-protein coding RNA 78, HCCAT1: hepatocellular carcinoma associated transcript 1 (non-protein coding) (HGNC:34232)

Characteristics

HULC RNA is ~500nuc, spliced and polyadenlyated,localized on human chromosome 6p24.3 and resembles the mammalian LTR transposon 1A. One striking feature of the HULC RNA sequence is the high density of stop codons in the small potential reading frames scattered throughout the HULC gene. It does not contain substantial open reading frames, and no protein product was detected. HULC is present in the cytoplasm, where it copurifies with ribosomes. The HULC gene includes a single intron and carries 1 canonical and 2 noncanonical polyadenylation signals 21 nt, 32 nt, and 47 nt, respectively, upstream from the polyA tail [1]

Function

HULC has a role in post-transcriptional modulation of gene expression. First clues about the function of HULC were obtained from siRNA-mediated knockdown of HULC in Hep3B and HepG2 cells, which resulted in a significant up- and down-regulation of several genes. [1] HULC may act as an endogenous ‘sponge’, which down-regulates a series of microRNAs (miRNAs) activities, including miR-372. Inhibition of miR-372 leads to reducing translational repression of its target gene, PRKACB, which in turn induces phosphorylation of CREB. [2]

Regulation

PKA pathway may involved in up-regulation of HULC. [2]

Expression

HULC Is specifically expressed in Hepatocytes and highly up-regulated in HCC. HULC is the first ncRNA with highly specific up-regulation in HCC. It was detected in blood of HCC patients therefore can be used as a potential biomarker. In contrast to the liver tumors, HULC is only slightly up-regulated in cirrhotic liver tissue and only barely detectable in most of the normal tissues. In situ hybridization revealed the specific and strong expression of HULC RNA in the cytoplasm of HCC, whereas it was not detected in tumor stroma and non-neoplastic liver cells. [1]

HULC was overexpressed in colorectal carcinomas that metastasize to the liver indicating that HULC expression is not confined to HCC. [3]

Experiment Forward primer Reverse primer
Quantiative RT-PCR 5'-atctgcaagccaggaagagtc- 3' 5'-cttgcttgatgctttggtctgt- 3'[1]

Diseases

  • Colorectal Carcinomas [3]
  • Hepatocellular Carcinoma [1]

Conservation

HLUC also present in other primates, gene shows good conservation above that of surrounding sequence. Not detected in rodents so may be primate specific [1]

Labs working on this lncRNA

  • Institute of Pathology, Medical University of Graz, Graz, Austria
  • Oridis-Biomed, Graz, Austria
  • Max F. Perutz Laboratories, Vienna, Austria
  • Laboratory of Experimental and Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
  • Department of Biology, Science and Technology, Alquds Abu-Dis University, Jerusalem, Israel.
  • Department of Laboratory Medicine, Ruijin Hospital, Faculty of Medical Laboratory Science, Department of Pathology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025

References

  1. 1.0 1.1 1.2 1.3 1.4 1.5 1.6 Panzitt K, Tschernatsch MMO, Guelly C, Moustafa T, Stradner M, Strohmaier HM et al. Characterization of HULC, a Novel Gene With Striking Up-Regulation in Hepatocellular Carcinoma, as Noncoding RNA[J]. Gastroenterology. 2007, 132(1):330-342.
  2. 2.0 2.1 Wang J, Liu X, Wu H, Ni P, Gu Z, Qiao Y et al. CREB up-regulates long non-coding RNA, HULC expression through interaction with microRNA-372 in liver cancer[J]. Nucleic acids research. 2010, 38(16):5366-5383.
  3. 3.0 3.1 Matouk IJ, Abbasi I, Hochberg A, Galun E, Dweik H & Akkawi M. Highly upregulated in liver cancer noncoding RNA is overexpressed in hepatic colorectal metastasis[J]. European Journal of gastroenterology & hepatology. 2009, 21(6):688-692.

Basic Information

Transcript ID

NONHSAT107640

Source

NONCODE4.0

Same with

,

Classification

intergenic

Length

500 nt

Genomic location

chr6+:8652442..8654459

Exon number

3

Exons

8652442..8652623,8653778..8654079,8654444..8654459

Genome context

Sequence
000001 ATGGGGGTGG AACTCATGAT GGAATTGGAG CCTTTACAAG GGAATGAAGA GACAAGAGCT CTCTTTATGC CACGTGAGGA 000080
000081 TACAGCAAGG CCCCAATCTG CAAGCCAGGA AGAGTCGTCA CGAGAACCAG ACCATGCAGG AACTCTGATC GTGGACATTT 000160
000161 CAACCTCCAG AACTGTGATC CAAAATGCAT ATGTATCTTT GGAAGAAACT CTGAAGTAAA GGCCGGAATA TTCTTTGTTT 000240
000241 AAAACATTAA AAACAAAACA GACCAAAGCA TCAAGCAAGA AGTTTCCTGG CAATAAACTA AGCACAGCAT TATTTTTTAA 000320
000321 GGAACACAAA TTAAGTGTTC AACCTGTGGC AAATTTGTAC TTTCTCCCTG AATTATGTTG TTATCAAAGA AAAAAATTGG 000400
000401 GAAGCATGGC AAAATATCAT CAAAACTGAA ACTAGAATTA AACAAAACTA AATTAAAATG AAATAAAATG ATGTCCATTC 000480
000481 TTAAAAAAAA AAAAAAAAAA
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