TCONS 00090092 MEG3

From LncRNAWiki
Revision as of 07:37, 23 November 2018 by Fatima (talk | contribs) (Regulation)
Jump to: navigation, search

MEG3, Maternally Expressed 3 is a long noncoding RNA gene that has been demonstrated to be a tumour suppressor in many malignancies.

Annotation

Name

TCONS_00090092_MEG3

Alias

GTL2; NCRNA00023; LINC00023; onco-lncRNA-83; non-protein coding RNA 23; long intergenic non-protein coding RNA 23 (HGNC:14575)

Characteristics

MEG3 is an imprinted gene maternally expressed in humans that encodes a long non-coding RNA of ∼1700 nucleotides. [1] MEG3 is located at 14q32.3. Although a location for a tumor suppressor gene has been hypothesized in this region because it is frequently lost in cholangiocarcinoma or neuroblastoma, no protein-coding gene has been identified so far at this site. [2] There are 12 different MEG3 gene transcripts, generated by alternative splicing. They contain the common exons 1-3 and exons 8-10, but each uses one or more exons 4-7 in a different combination in the middle. MEG3 isoform expression patterns are tissue and cell type specific.[3]

Function

MEG3 functions an important role in the regulation of proper cell growth and embryo development and therefore may be a putative tumor suppressor gene, because one of its functions is to activate p53 and inhibit cell proliferation. [3] MEG3 can also control gene expression at imprinted loci through recruitment of the polycomb repressive complex 2 (PRC2). [4]

Regulation

Through studies, a functional tissue-specific mechanism of regulation of MEG3 expression via microRNA-29a-dependent regulation of promoter methylation was reported. Overexpression of mir-29a increased expression of MEG3. [5]

Expression

The aberrant expression of this lncRNA has been linked to hepatoblastoma development.[5] Microarray analysis revealedMEG3 was downregulated by 210-fold in in malignant hepatocytes relative to expression in non-malignant hepatocytes. MEG3 expression was markedly reduced in four human hepatocellular cancer (HCC) cell lines compared with normal hepatocytes by real-time PCR. RNA In situhybridization showed intense cytoplasmic expression of MEG3 in non-neoplastic liver with absent or very weak expression in HCC tissues. [5]

Experiment Forward primer Reverse primer
qRT-PCR 5'-ACACTTGCTGTCTTCCTT- 3' 5'-CCAGGTCAGGAACTTTGT- 3'[6]

Diseases

  • Cholangiocarcinoma [2]
  • Hepatoblasoma [6]
  • Pancreatic cancer [7]


Sequence

>gi|55384|ref|NR_046470.2| Homo sapiens maternally expressed 3 (MEG3), transcript variant 13, long non-coding RNA

000001 AGCCCCTAGC GCAGACGGCG GAGAGCAGAG AGGGAGCGCG CCTTGGCTCG CTGGCCTTGG CGGCGGCTCC TCAGGAGAGC 000080
000081 TGGGGCGCCC ACGAGAGGAT CCCTCACCCG GGTCTCTCCT CAGGGATGAC ATCATCCGTC CACCTCCTTG TCTTCAAGGA 000160
000161 CCACCTCCTC TCCATGCTGA GCTGCTGCCA AGGGGCCTGC TGCCCATCTA CACCTCACGA GGGCACTAGG AGCACGGTTT 000240
000241 CCTGGATCCC ACCAACATAC AAAGCAGCCA CTCACTGACC CCCAGGACCA GGATGGCAAA GGATGAAGAG GACCGGAACT 000320
000321 GACCAGCCAG CTGTCCCTCT TACCTAAAGA CTTAAACCAA TGCCCTAGTG AGGGGGCATT GGGCATTAAG CCCTGACCTT 000400
000401 TGCTATGCTC ATACTTTGAC TCTATGAGTA CTTTCCTATA AGTCTTTGCT TGTGTTCACC TGCTAGCAAA CTGGAGTGTT 000480
000481 TCCCTCCCCA AGGGGGTGTC AGTCTTTGTC GACTGACTCT GTCATCACCC TTATGATGTC CTGAATGGAA GGATCCCTTT 000560
000561 GGGAAATTCT CAGGAGGGGG ACCTGGGCCA AGGGCTTGGC CAGCATCCTG CTGGCAACTC CAAGGCCCTG GGTGGGCTTC 000640
000641 TGGAATGAGC ATGCTACTGA ATCACCAAAG GCACGCCCGA CCTCTCTGAA GATCTTCCTA TCCTTTTCTG GGGGAATGGG 000720
000721 GTCGATGAGA GCAACCTCCT AGGGTTGTTG TGAGAATTAA ATGAGATAAA AGAGGCCTCA GGCAGGATCT GGCATAGAGG 000800
000801 AGGTGATCAG CAAATGTTTG TTGAAAAGGT TTGACAGGTC AGTCCCTTCC CACCCCTCTT GCTTGTCTTA CTTGTCTTAT 000880
000881 TTATTCTCCA ACAGCACTCC AGGCAGCCCT TGTCCACGGG CTCTCCTTGC ATCAGGGCTA ATCTCGGGCC TTGTCGAAGG 000960
000961 AAGAGGCTGC AGACGTTAAT GAGGTTAGCT GCTGGATTCC AGTATTCGTC GCATAAGGAT CCTTCTTTGT CTGCGAAGGA 001040
001041 AAAACACACT GATTATCATA ATGAGCAGGT TCCCAGTGCC CCCGACAAGC CCCTGCTGGT GTCTCCATCT CCTGCCAAGC 001120
001121 ATCCTCCAGT GCCTCCTCCT GTGGGCCTGG CCTCAGGGCT ATGGACAGAC TCCTGTCCCA TCCCAGAGAC CCCTCGTGAT 001200
001201 CGTGCCCTGG CACGTGGGCC GTGGCCCGGC TGGGTCGGCT GAAGAACTGC GGATGGAAGC TGCGGAAGAG GCCCTGATGG 001280
001281 GGCCCACCAT CCCGGACCCA AGTCTTCTTC CTGGCGGGCC TCTCGTCTCC TTCCTGGTTT GGGCGGAAGC CATCACCTGG 001360
001361 ATGCCTACGT GGGAAGGGAC CTCGAATGTG GGACCCCAGC CCCTCTCCAG CTCGAAATCC CTCCACAGCC ACGGGGACAC 001440
001441 CCTGCACCTA TTCCCACGGG ACAGGCTGGA CCCAGAGACT CTGGACCCGG GGCCTCCCCT TGAGTAGAGA CCCGCCCTCT 001520
001521 GACTGATGGA CGCCGCTGAC CTGGGGTCAG ACCCGTGGGC TGGACCCCTG CCCACCCCGC AGGAACCCTG AGGCCTAGGG 001600
001601 GAGCTGTTGA GCCTTCAGTG TCTGCATGTG GGAAGTGGGC TCCTTCACCT ACCTCACAGG GCTGTTGTGA GGGGCGCTGT 001680
001681 GATGCGGTTC CAAAGCACAG GGCTTGGCGC ACCCCACTGT GCTCTCAATA AATGTGTTTC CTGTCTTAAC AAAAAAAAAA 001760
001761 AAAAAAAAAA AAAAAAAAAA AAAAA

Labs Working

  • Neuroendocrine Unit and the Neuropathology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114
  • Department of Pathology, Hôpital Beaujon, AP-HP, 92110 Clichy, France
  • College of Medicine, and the Ohio State University Comprehensive Cancer Center, Ohio State University, Columbus, OH, USA
  • Mayo Clinic, Jacksonville, FL, USA
  • Department of Pediatric Surgery, Children's Hospital of Fudan University and The Key Laboratory of Neonatal Disease, Chinese Ministry of Health, Shanghai, China

References

  1. Zhou, Y., Zhong, Y., Wang, Y., Zhang, X., Batista, D. L., Gejman, R., ... & Klibanski, A. Activation of p53 by MEG3 non-coding RNA[J]. Journal of Biological Chemistry. 2007,282(34): 24731-24742.
  2. 2.0 2.1 Cazals-Hatem D, Rebouissou S, Bioulac-Sage P, Bluteau O, Blanché H, Franco D et al. Clinical and molecular analysis of combined hepatocellular-cholangiocarcinomas[J]. Journal of Hepatology. 2004,41(2):292-298.
  3. 3.0 3.1 Zhang X, Rice K, Wang Y, Chen W, Zhong Y, Nakayama Y et al. Maternally expressed gene 3 (MEG3) noncoding ribonucleic acid: isoform structure, expression, and functions[J]. Endocrinology. 2010,151(3):939-947.
  4. Prensner JR & Chinnaiyan AM. The emergence of lncRNAs in cancer biology[J]. Cancer discovery. 2011, 1(5):391-407.
  5. 5.0 5.1 5.2 Braconi C, Kogure T, Valeri N, Huang N, Nuovo G, Costinean S et al. microRNA-29 can regulate expression of the long non-coding RNA gene MEG3 in hepatocellular cancer[J]. Oncogene. 2011,30:4750-4756.
  6. 6.0 6.1 Dong R, Jia D, Xue P, Cui X, Li K, Zheng S et al. Genome-wide analysis of long noncoding RNA (lncRNA) expression in hepatoblastoma tissues[J]. Plos One. 2014, 9(1):e85599-e85599.
  7. Ma L, Wang F, Du C, et al. Long non-coding RNA MEG3 functions as a tumour suppressor and has prognostic predictive value in human pancreatic cancer[J]. Oncology reports. 2018,39(3):1132-1140.