MALAT1

MALAT 1 (metastasis associated lung adenocarcinoma transcript 1) also known as NEAT2 (noncoding nuclear-enriched abundant transcript 2) is a large, infrequently spliced non-coding RNA, which is highly conserved amongst mammals and highly expressed in the nucleus.[3] MALAT1 was identified in multiple types of physiological processes, such as alternative splicing, nuclear organization, epigenetic modulating of gene expression, and a number of evidences indicate that MALAT1 also closely relate to various pathological processes, ranging from diabetes complications to cancers.[4][5] It regulates the expression of metastasis-associated genes.[6] It also positively regulates cell motility via the transcriptional and/or post-transcriptional regulation of motility-related genes.[7] MALAT1 may play a role in temperature-dependent sex determination in the Red-eared slider turtle (Trachemys scripta).[8]

MALAT1
Identifiers
AliasesMALAT1, HCN, LINC00047, MALAT-1, NCRNA00047, NEAT2, PRO2853, mascRNA, metastasis associated lung adenocarcinoma transcript 1 (non-protein coding), metastasis associated lung adenocarcinoma transcript 1
External IDsOMIM: 607924 GeneCards: MALAT1
Gene location (Human)
Chr.Chromosome 11 (human)[1]
Band11q13.1Start65,497,688 bp[1]
End65,506,516 bp[1]
Orthologs
SpeciesHumanMouse
Entrez

378938

n/a

Ensembl

ENSG00000251562

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UniProt

n/a

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RefSeq (mRNA)

n/a

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RefSeq (protein)

n/a

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Location (UCSC)Chr 11: 65.5 – 65.51 Mbn/a
PubMed search[2]n/a
Wikidata
View/Edit Human
Conserved secondary structure in Metastasis associated lung adenocarcinoma transcript 1
Predicted secondary structure and sequence conservation of MALAT1
Identifiers
SymbolMALAT1
RfamRF01871
Other data
RNA typeGene;
Domain(s)Eukaryota;
GO2000147
SO0001263
PDB structuresPDBe

Expression in alcoholic brains

Transcripts of MALAT1 are significantly increased in the cerebellum of human alcoholics, as well as in similar regions of rat brains after the withdrawal of ethanol vapours. This alcohol-induced upregulation of MALAT1 may be responsible for differential expression of a number of proteins which contribute to ethanol tolerance and dependency in humans.[9]

Prognostic potential in cancer

The implication of MALAT1 RNA in the pathology of various cancers has been documented.[5] Elevated MALAT1 expression is correlated with poor overall survival in various types of cancer, suggesting that this gene is a prognostic factor for different types of cancer.[10][11]

As a target for the treatment of cancer

Genetic loss or systemic knockdown of Malat1 using antisense oligonucleotides (ASO) in the mouse mammary carcinoma model results in slower tumor growth accompanied by significant differentiation into cystic tumors and a reduction in metastasis. At the molecular level, the ASO-Malat1 hybrid stimulates a naturally occurring cellular enzyme that degrades the Malat1 lncRNA. Malat1 knockdown results in alterations in gene expression and changes in splicing patterns of genes involved in differentiation and protumorigenic signaling pathways. Metastatic tumors have a dependency on Malat1—they can't thrive without it. And very importantly, only the cancer cells seem to require it. In so far as MALAT1 has been identified to be involved in tumorigenesis of various types of cancer such as lung cancer, pancreatic cancer, cervical cancer Malat1 ASOs represent a potential therapy for inhibiting such cancers progression.[12]

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gollark: No, it just doesn't have network I/O.
gollark: Oh, it can, it works perfectly.
gollark: www. is bad.

See also

References
  1. GRCh38: Ensembl release 89: ENSG00000251562 - Ensembl, May 2017
  2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. Hutchinson JN, Ensminger AW, Clemson CM, Lynch CR, Lawrence JB, Chess A (2007). "A screen for nuclear transcripts identifies two linked noncoding RNAs associated with SC35 splicing domains". BMC Genomics. 8: 39. doi:10.1186/1471-2164-8-39. PMC 1800850. PMID 17270048.
  4. Wu Y, Huang C, Meng X, Li J (2015). "Long Noncoding RNA MALAT1: Insights into its Biogenesis and Implications in Human Disease". Current Pharmaceutical Design. 21 (34): 5017–5028. doi:10.2174/1381612821666150724115625. PMID 26205289.
  5. Yoshimoto R, Mayeda A, Yoshida M, Nakagawa S (January 2016). "MALAT1 long non-coding RNA in cancer". Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms. 1859 (1): 192–199. doi:10.1016/j.bbagrm.2015.09.012. PMID 26434412.
  6. Gutschner T, Hämmerle M, Eissmann M, Hsu J, Kim Y, Hung G, Revenko A, Arun G, Stentrup M, Gross M, Zörnig M, MacLeod AR, Spector DL, Diederichs S (February 2013). "The noncoding RNA MALAT1 is a critical regulator of the metastasis phenotype of lung cancer cells". Cancer Research. 73 (3): 1180–1189. doi:10.1158/0008-5472.CAN-12-2850. PMC 3589741. PMID 23243023.
  7. Tano K, Mizuno R, Okada T, Rakwal R, Shibato J, Masuo Y, Ijiri K, Akimitsu N (November 2010). "MALAT-1 enhances cell motility of lung adenocarcinoma cells by influencing the expression of motility-related genes". FEBS Letters. 584 (22): 4575–4580. doi:10.1016/j.febslet.2010.10.008. PMID 20937273.
  8. Chojnowski JL, Braun EL (Jul 15, 2012). "An unbiased approach to identify genes involved in development in a turtle with temperature-dependent sex determination". BMC Genomics. 13: 308. doi:10.1186/1471-2164-13-308. PMC 3434017. PMID 22793670.
  9. Kryger R, Fan L, Wilce PA, Jaquet V (November 2012). "MALAT-1, a non protein-coding RNA is upregulated in the cerebellum, hippocampus and brain stem of human alcoholics". Alcohol. 46 (7): 629–634. doi:10.1016/j.alcohol.2012.04.002. PMID 22560368.
  10. Tian X, Xu G (2015). "Clinical value of lncRNA MALAT1 as a prognostic marker in human cancer: systematic review and meta-analysis". BMJ Open. 5 (9): e008653. doi:10.1136/bmjopen-2015-008653. PMC 4593150. PMID 26423854.
  11. Wei Y, Niu B (2015). "Role of MALAT1 as a Prognostic Factor for Survival in Various Cancers: A Systematic Review of the Literature with Meta-Analysis". Disease Markers. 2015: 164635. doi:10.1155/2015/164635. PMC 4572489. PMID 26420912.
  12. Arun G, Diermeier S, Akerman M, Chang KC, Wilkinson JE, Hearn S, Kim Y, MacLeod AR, Krainer AR, Norton L, Brogi E, Egeblad M, Spector DL (January 2016). "Differentiation of mammary tumors and reduction in metastasis upon Malat1 lncRNA loss". Genes & Development. 30 (1): 34–51. doi:10.1101/gad.270959.115. PMC 4701977. PMID 26701265.

Further reading
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