Biology:MALAT1
 Generic protein structure example |
| 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 | 2000147 |
| SO | 0001263 |
| PDB structures | PDBe |
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.[1] 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.[2][3] It regulates the expression of metastasis-associated genes.[4] It also positively regulates cell motility via the transcriptional and/or post-transcriptional regulation of motility-related genes.[5] MALAT1 may play a role in temperature-dependent sex determination in the Red-eared slider turtle (Trachemys scripta).[6]
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.[7]
Prognostic potential in cancer
The implication of MALAT1 RNA in the pathology of various cancers has been documented.[3] 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.[8][9]
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.[10]
See also
References
- ↑ "A screen for nuclear transcripts identifies two linked noncoding RNAs associated with SC35 splicing domains". BMC Genomics 8: 39. 2007. doi:10.1186/1471-2164-8-39. PMID 17270048.
- ↑ "Long Noncoding RNA MALAT1: Insights into its Biogenesis and Implications in Human Disease". Current Pharmaceutical Design 21 (34): 5017–5028. 2015. doi:10.2174/1381612821666150724115625. PMID 26205289.
- ↑ 3.0 3.1 "MALAT1 long non-coding RNA in cancer". Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms 1859 (1): 192–199. January 2016. doi:10.1016/j.bbagrm.2015.09.012. PMID 26434412.
- ↑ "The noncoding RNA MALAT1 is a critical regulator of the metastasis phenotype of lung cancer cells". Cancer Research 73 (3): 1180–1189. February 2013. doi:10.1158/0008-5472.CAN-12-2850. PMID 23243023.
- ↑ "MALAT-1 enhances cell motility of lung adenocarcinoma cells by influencing the expression of motility-related genes". FEBS Letters 584 (22): 4575–4580. November 2010. doi:10.1016/j.febslet.2010.10.008. PMID 20937273.
- ↑ "An unbiased approach to identify genes involved in development in a turtle with temperature-dependent sex determination". BMC Genomics 13: 308. Jul 15, 2012. doi:10.1186/1471-2164-13-308. PMID 22793670.
- ↑ "MALAT-1, a non protein-coding RNA is upregulated in the cerebellum, hippocampus and brain stem of human alcoholics". Alcohol 46 (7): 629–634. November 2012. doi:10.1016/j.alcohol.2012.04.002. PMID 22560368.
- ↑ "Clinical value of lncRNA MALAT1 as a prognostic marker in human cancer: systematic review and meta-analysis". BMJ Open 5 (9): e008653. 2015. doi:10.1136/bmjopen-2015-008653. PMID 26423854.
- ↑ "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. 2015. doi:10.1155/2015/164635. PMID 26420912.
- ↑ "Differentiation of mammary tumors and reduction in metastasis upon Malat1 lncRNA loss". Genes & Development 30 (1): 34–51. January 2016. doi:10.1101/gad.270959.115. PMID 26701265.
Further reading
- "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. March 2010. doi:10.1093/abbs/gmq008. PMID 20213048.
- "Resveratrol inhibits invasion and metastasis of colorectal cancer cells via MALAT1 mediated Wnt/β-catenin signal pathway". PLOS ONE 8 (11): e78700. Nov 2013. doi:10.1371/journal.pone.0078700. PMID 24244343. Bibcode: 2013PLoSO...878700J.
- "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. November 2009. doi:10.1093/molehr/gap071. PMID 19690017.
- "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. May 2000. doi:10.1006/geno.2000.6194. PMID 10843802.
- "Oxytocin stimulates expression of a noncoding RNA tumor marker in a human neuroblastoma cell line". Life Sciences 86 (11–12): 455–460. March 2010. doi:10.1016/j.lfs.2010.02.001. PMID 20149803.
- "A transcript map for the 2.8-Mb region containing the multiple endocrine neoplasia type 1 locus". Genome Research 7 (7): 725–735. July 1997. doi:10.1101/gr.7.7.725. PMID 9253601.
- "The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation". Molecular Cell 39 (6): 925–938. September 2010. doi:10.1016/j.molcel.2010.08.011. PMID 20797886.
- "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. July 2003. doi:10.1093/hmg/ddg178. PMID 12837690.
- "Phenotypic characterization of endometrial stromal sarcoma of the uterus". Cancer Science 97 (2): 106–112. February 2006. doi:10.1111/j.1349-7006.2006.00147.x. PMID 16441420.
- "3′ end processing of a long nuclear-retained noncoding RNA yields a tRNA-like cytoplasmic RNA". Cell 135 (5): 919–932. November 2008. doi:10.1016/j.cell.2008.10.012. PMID 19041754.
- "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. September 2003. doi:10.1038/sj.onc.1206928. PMID 12970751.
- "Identification of cis- and trans-acting factors involved in the localization of MALAT-1 noncoding RNA to nuclear speckles". RNA 18 (4): 738–751. April 2012. doi:10.1261/rna.028639.111. PMID 22355166.
External links
- OMIM page for MALAT1
- HGNC page for MALAT1
- Page for Metastasis associated lung adenocarcinoma transcript 1 at Rfam
- Relevance of MALAT1 in single-cell RNA sequencing data
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