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 | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Aliases | MALAT1, HCN, LINC00047, MALAT-1, NCRNA00047, NEAT2, PRO2853, mascRNA, metastasis associated lung adenocarcinoma transcript 1 (non-protein coding), metastasis associated lung adenocarcinoma transcript 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 607924 GeneCards: MALAT1 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||||||||||
| Conserved secondary structure in Metastasis associated lung adenocarcinoma transcript 1 | |
|---|---|
 Predicted secondary structure and sequence conservation of MALAT1 | |
| Identifiers | |
| Symbol | MALAT1 |
| Rfam | RF01871 |
| Other data | |
| RNA type | Gene; |
| Domain(s) | Eukaryota; |
| GO | GO:2000147 |
| SO | SO:0001263 |
| PDB structures | PDBe |
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]
References
- GRCh38: Ensembl release 89: ENSG00000251562 - Ensembl, May 2017
- "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- 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.
- 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.
- 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.
- 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.
- 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. S2CID 207575862.
- 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.
- 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.
- 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.
- 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.
- 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
- Guo F, Li Y, Liu Y, Wang J, Li Y, Li G (March 2010). "Inhibition of metastasis-associated lung adenocarcinoma transcript 1 in CaSki human cervical cancer cells suppresses cell proliferation and invasion". Acta Biochimica et Biophysica Sinica. 42 (3): 224–229. doi:10.1093/abbs/gmq008. PMID 20213048.
- Ji Q, Liu X, Fu X, Zhang L, Sui H, Zhou L, Sun J, Cai J, Qin J, Ren J, Li Q (Nov 2013). "Resveratrol inhibits invasion and metastasis of colorectal cancer cells via MALAT1 mediated Wnt/β-catenin signal pathway". PLOS ONE. 8 (11): e78700. Bibcode:2013PLoSO...878700J. doi:10.1371/journal.pone.0078700. PMC 3823921. PMID 24244343.
- Tseng JJ, Hsieh YT, Hsu SL, Chou MM (November 2009). "Metastasis associated lung adenocarcinoma transcript 1 is up-regulated in placenta previa increta/percreta and strongly associated with trophoblast-like cell invasion in vitro". Molecular Human Reproduction. 15 (11): 725–731. doi:10.1093/molehr/gap071. PMID 19690017.
- van Asseldonk M, Schepens M, de Bruijn D, Janssen B, Merkx G, Geurts van Kessel A (May 2000). "Construction of a 350-kb sequence-ready 11q13 cosmid contig encompassing the markers D11S4933 and D11S546: mapping of 11 genes and 3 tumor-associated translocation breakpoints". Genomics. 66 (1): 35–42. doi:10.1006/geno.2000.6194. PMID 10843802.
- Koshimizu TA, Fujiwara Y, Sakai N, Shibata K, Tsuchiya H (March 2010). "Oxytocin stimulates expression of a noncoding RNA tumor marker in a human neuroblastoma cell line". Life Sciences. 86 (11–12): 455–460. doi:10.1016/j.lfs.2010.02.001. PMID 20149803.
- Guru SC, Agarwal SK, Manickam P, Olufemi SE, Crabtree JS, Weisemann JM, Kester MB, Kim YS, Wang Y, Emmert-Buck MR, Liotta LA, Spiegel AM, Boguski MS, Roe BA, Collins FS, Marx SJ, Burns L, Chandrasekharappa SC (July 1997). "A transcript map for the 2.8-Mb region containing the multiple endocrine neoplasia type 1 locus". Genome Research. 7 (7): 725–735. doi:10.1101/gr.7.7.725. PMC 310681. PMID 9253601.
- Tripathi V, Ellis JD, Shen Z, Song DY, Pan Q, Watt AT, Freier SM, Bennett CF, Sharma A, Bubulya PA, Blencowe BJ, Prasanth SG, Prasanth KV (September 2010). "The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation". Molecular Cell. 39 (6): 925–938. doi:10.1016/j.molcel.2010.08.011. PMC 4158944. PMID 20797886.
- Kuiper RP, Schepens M, Thijssen J, van Asseldonk M, van den Berg E, Bridge J, Schuuring E, Schoenmakers EF, van Kessel AG (July 2003). "Upregulation of the transcription factor TFEB in t(6;11)(p21;q13)-positive renal cell carcinomas due to promoter substitution". Human Molecular Genetics. 12 (14): 1661–1669. doi:10.1093/hmg/ddg178. PMID 12837690.
- Yamada K, Kano J, Tsunoda H, Yoshikawa H, Okubo C, Ishiyama T, Noguchi M (February 2006). "Phenotypic characterization of endometrial stromal sarcoma of the uterus". Cancer Science. 97 (2): 106–112. doi:10.1111/j.1349-7006.2006.00147.x. PMID 16441420. S2CID 25815889.
- Wilusz JE, Freier SM, Spector DL (November 2008). "3′ end processing of a long nuclear-retained noncoding RNA yields a tRNA-like cytoplasmic RNA". Cell. 135 (5): 919–932. doi:10.1016/j.cell.2008.10.012. PMC 2722846. PMID 19041754.
- Ji P, Diederichs S, Wang W, Böing S, Metzger R, Schneider PM, Tidow N, Brandt B, Buerger H, Bulk E, Thomas M, Berdel WE, Serve H, Müller-Tidow C (September 2003). "MALAT-1, a novel noncoding RNA, and thymosin beta4 predict metastasis and survival in early-stage non-small cell lung cancer". Oncogene. 22 (39): 8031–8041. doi:10.1038/sj.onc.1206928. PMID 12970751.
- Miyagawa R, Tano K, Mizuno R, Nakamura Y, Ijiri K, Rakwal R, Shibato J, Masuo Y, Mayeda A, Hirose T, Akimitsu N (April 2012). "Identification of cis- and trans-acting factors involved in the localization of MALAT-1 noncoding RNA to nuclear speckles". RNA. 18 (4): 738–751. doi:10.1261/rna.028639.111. PMC 3312561. PMID 22355166.