MALAT 1 (metastasis associated lung adenocarcinoma transcript 1) also known as NEAT2 (noncoding nuclear-enriched abundant transcript 2) is a large, infrequently splicednon-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]
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]
↑ 3.03.1Yoshimoto R, Mayeda A, Yoshida M, Nakagawa S (January 2016). "MALAT1 long non-coding RNA in cancer". Biochimica et Biophysica Acta. 1859 (1): 192–9. doi:10.1016/j.bbagrm.2015.09.012. PMID26434412.
↑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): 629–34. doi:10.1016/j.alcohol.2012.04.002. PMID22560368.
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): 224–9. doi:10.1093/abbs/gmq008. PMID20213048.
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. doi:10.1371/journal.pone.0078700. open access publication – free to read
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): 725–31. doi:10.1093/molehr/gap071. PMID19690017.
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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): 455–60. doi:10.1016/j.lfs.2010.02.001. PMID20149803.
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): 925–38. doi:10.1016/j.molcel.2010.08.011. PMID20797886.
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): 1661–9. doi:10.1093/hmg/ddg178. PMID12837690.
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): 106–12. doi:10.1111/j.1349-7006.2006.00147.x. PMID16441420.
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): 8031–41. doi:10.1038/sj.onc.1206928. PMID12970751.
