MALAT-1 is overexpressed in many kinds of cancers and is closely associated with tumor growth and metastasis.
Malat1: Metastasis-associated lung adenocarcinoma transcript 1
Neat2: Nuclear enriched abundant transcript 2
Malat1 gene is localized in the intergenic region of the genome. It is about 8kb in length and the transcript has only one exon . The 3’-end of the transcript is a conserved tRNA-like sequence, which can be modified by RNase P and cleaved by RNase Z to yield another ncRNA (61nt), the cytoplasmic MALAT1-associated small cytoplasmic RNA (mascRNA) .
Malat1 is stable in human B cells (half-life: 16.5 h)  and Hela cells (half-life: about 7 h) , but is unstable in mouse 3T3 cells (half-life: 3 h)  and N2A cells ( half-life: 4 h) . MALAT-1 is generally stable in cancer cells, with the half-life ranging from ~ 9 h to > 12 h in various cancer cells . Xrn2, PM/Scl-75, PARN, and Mtr4, known nuclear RNases or RNA helicases, do not affect MALAT-1 degradation .
MALAT-1 localizes predominately in the nucleus . In G2/M cell cycle phase, MALAT-1 transcripts partially translocate from the nucleus into the cytoplasm . RNPS1, SRm160, and IBP160 are found to contribute to the nuclear localization of MALAT-1 .
MALAT-1 localizes specifically in the SC35 splicing domains in the nucleus, suggesting its function in pre-mRNA metabolism or specific nuclear structures . The later studies found that MALAT-1 could modulate mRNA alternative splicing via its interaction with the serine/arginine-rich (SR) family of nuclear phosphoproteins that are involved in the splicing machinery . MALAT-1 regulates synapse formation by modulating the expression of genes involved in synapse formation and/or maintenance . However, splicing alterations were not found after Malat1 ablation in mice . Also, MALAT1 does not alter alternative splicing but actively regulates gene expression including a set of metastasis-associated genes in lung cancer cells . These results indicate that alternative functions for MALAT-1 may exist.
MALAT-1 can function by participating in localization of important proteins, such as hnRNP C  and growth control genes . MALAT-1 is found to regulate cell cycle progress in G2/M phase , G1/S phase , and G0/G1 phase . In the G2/M phase, MALAT-1 interacts with hnRNP C to facilitate the cytoplasmic translocation of hnRNP C, leading to cell cycle progresion . MALAT1 could interact with the demethylated form of CBX4 (chromobox homolog 4), and controls the relocalization of growth control genes between polycomb bodies and interchromatin granules . MALAT1 could bind to Human PSF (hPSF) protein to release hPSF from a repressed proto-oncogene and activate transcription, driving transformation and tumorigenesis .
MALAT-1 regulates synaptogenesis and is involved in the development of advanced invasive placentation . Deregulation of MALAT-1 is found to be closely associated with the development of cancer. In vitro, it is found that MALAT-1 promotes epithelial–mesenchymal transition (EMT) of bladder cancer cells by activating Wnt signaling . 3' end of MALAT-1 (6918 nt-8441 nt) is found to be important in colorectal cancer metastasis . In lung adenocarcinoma cells, MALAT-1 may regulate cell motility through transcriptional and post-transcriptional regulation of motility related gene expression . However, mechanisms of these functions are not clear.
MALAT-1 is over-expressed in many human carcinomas, including those of the breast, pancreas, lung, colon, prostate, and liver .
It is also found to be up-regulated in the cerebellum, hippocampus and brain stem of human alcoholics .
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In breast cancer cells, high concentration E2 treatment largely decreases MALAT-1 RNA level in an ERa independent way .
Disruption of p53 appears to play an important role in the up-regulation of MALAT-1 .
CREB (cyclic AMP-responsive element binding) transcription factor is found to bind to the defined proximal promoter of the MALAT1 gene, leading to the up-regulation of MALAT1 .
MALAT-1 was first identified as a prognostic marker for metastasis and patient survival in non-small cell lung cancer (NSCLC) . It is found to be overexpressed in various tumors and cancer cell lines, including lung cancer , endometrial stromal sarcoma of the uterus , hepatocellular carcinomas , breast cancer , pancreas cancer , colon cancer , prostate cancer , melanoma , bladder cancer . Overexpression of MALAT-1 in cancer cells is closely associated with tumor growth and metastasis .
There is no significant difference in MALAT-1 lncRNA levels in normal pituitary tissues, invasive NFPAs (non-functioning pituitary adenomas), and non-invasive NFPAs, and no significant association between MALAT-1 expression and patient clinicopathological characteristics .
MALAT-1 is highly conserved across mammals . However, sequence conservation is limited in vertebrates. Sequence similarity between zebrafish and mammalian MALAT1 is restricted to the 3′ end, while the length of MALAT1 (~7 kb) along with the gene structure appeare to be roughly fixed in all vertebrates .
- hnRNP C 
- CBX4 (chromobox homolog 4) 
- Human PSF (hPSF) protein 
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Labs working on this lncRNA
- Department of Medicine, University of Münster, Germany
- Howard Hughes Medical Institute, University of California, San Diego, School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0648, USA
- Department of Urology, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, People's Republic of China
- Institute of Molecular Medicine and State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100871, China
- Ji, P., Diederichs, S., Wang, W., Boing, S., Metzger, R., Schneider, P.M., Tidow, N., Brandt, B., Buerger, H., Bulk, E. et al. (2003) MALAT-1, a novel noncoding RNA, and thymosin beta4 predict metastasis and survival in early-stage non-small cell lung cancer. Oncogene, 22, 8031-8041.
- Hutchinson, J.N., Ensminger, A.W., Clemson, C.M., Lynch, C.R., Lawrence, J.B. and Chess, A. (2007) A screen for nuclear transcripts identifies two linked noncoding RNAs associated with SC35 splicing domains. BMC Genomics, 8, 39.
- Wilusz, J.E., Freier, S.M. and Spector, D.L. (2008) 3' end processing of a long nuclear-retained noncoding RNA yields a tRNA-like cytoplasmic RNA. Cell, 135, 919-932.
- Clark, M.B., Johnston, R.L., Inostroza-Ponta, M., Fox, A.H., Fortini, E., Moscato, P., Dinger, M.E. and Mattick, J.S. (2012) Genome-wide analysis of long noncoding RNA stability. Genome Res, 22, 885-898.
- Tani, H., Mizutani, R., Salam, K.A., Tano, K., Ijiri, K., Wakamatsu, A., Isogai, T., Suzuki, Y. and Akimitsu, N. (2012) Genome-wide determination of RNA stability reveals hundreds of short-lived noncoding transcripts in mammals. Genome Res, 22, 947-956.
- Tani, H., Nakamura, Y., Ijiri, K. and Akimitsu, N. (2010) Stability of MALAT-1, a nuclear long non-coding RNA in mammalian cells, varies in various cancer cells. Drug Discov Ther, 4, 235-239.
- Yang, F., Yi, F., Han, X., Du, Q. and Liang, Z. (2013) MALAT-1 interacts with hnRNP C in cell cycle regulation. FEBS Lett, 587, 3175-3181.
- Miyagawa, R., Tano, K., Mizuno, R., Nakamura, Y., Ijiri, K., Rakwal, R., Shibato, J., Masuo, Y., Mayeda, A., Hirose, T. et al. (2012) Identification of cis- and trans-acting factors involved in the localization of MALAT-1 noncoding RNA to nuclear speckles. RNA, 18, 738-751.
- Tripathi, V., Ellis, J.D., Shen, Z., Song, D.Y., Pan, Q., Watt, A.T., Freier, S.M., Bennett, C.F., Sharma, A., Bubulya, P.A. et al. (2010) The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation. Mol Cell, 39, 925-938.
- Bernard, D., Prasanth, K.V., Tripathi, V., Colasse, S., Nakamura, T., Xuan, Z., Zhang, M.Q., Sedel, F., Jourdren, L., Coulpier, F. et al. (2010) A long nuclear-retained non-coding RNA regulates synaptogenesis by modulating gene expression. EMBO J, 29, 3082-3093.
- Zhang, B., Arun, G., Mao, Y.S., Lazar, Z., Hung, G., Bhattacharjee, G., Xiao, X., Booth, C.J., Wu, J., Zhang, C. et al. (2012) The lncRNA Malat1 is dispensable for mouse development but its transcription plays a cis-regulatory role in the adult. Cell Rep, 2, 111-123.
- Gutschner, T., Hammerle, M., Eissmann, M., Hsu, J., Kim, Y., Hung, G., Revenko, A., Arun, G., Stentrup, M., Gross, M. et al. (2013) The noncoding RNA MALAT1 is a critical regulator of the metastasis phenotype of lung cancer cells. Cancer Res, 73, 1180-1189.
- Yang, L., Lin, C., Liu, W., Zhang, J., Ohgi, K.A., Grinstein, J.D., Dorrestein, P.C. and Rosenfeld, M.G. (2011) ncRNA- and Pc2 methylation-dependent gene relocation between nuclear structures mediates gene activation programs. Cell, 147, 773-788.
- Ulitsky, I., Shkumatava, A., Jan, C.H., Sive, H. and Bartel, D.P. (2011) Conserved function of lincRNAs in vertebrate embryonic development despite rapid sequence evolution. Cell, 147, 1537-1550.
- Ren, S., Liu, Y., Xu, W., Sun, Y., Lu, J., Wang, F., Wei, M., Shen, J., Hou, J., Gao, X. et al. (2013) Long noncoding RNA MALAT-1 is a new potential therapeutic target for castration resistant prostate cancer. J Urol, 190, 2278-2287.
- Li, L., Feng, T., Lian, Y., Zhang, G., Garen, A. and Song, X. (2009) Role of human noncoding RNAs in the control of tumorigenesis. Proc Natl Acad Sci U S A, 106, 12956-12961.
- Tseng, J.J., Hsieh, Y.T., Hsu, S.L. and Chou, M.M. (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. Mol Hum Reprod, 15, 725-731.
- Ying, L., Chen, Q., Wang, Y., Zhou, Z., Huang, Y. and Qiu, F. (2012) Upregulated MALAT-1 contributes to bladder cancer cell migration by inducing epithelial-to-mesenchymal transition. Mol Biosyst, 8, 2289-2294.
- Xu, C., Yang, M., Tian, J., Wang, X. and Li, Z. (2011) MALAT-1: a long non-coding RNA and its important 3' end functional motif in colorectal cancer metastasis. Int J Oncol, 39, 169-175.
- Tano, K., Mizuno, R., Okada, T., Rakwal, R., Shibato, J., Masuo, Y., Ijiri, K. and Akimitsu, N. (2010) MALAT-1 enhances cell motility of lung adenocarcinoma cells by influencing the expression of motility-related genes. FEBS Lett, 584, 4575-4580.
- Lin, R., Maeda, S., Liu, C., Karin, M. and Edgington, T.S. (2007) A large noncoding RNA is a marker for murine hepatocellular carcinomas and a spectrum of human carcinomas. Oncogene, 26, 851-858.
- Kryger, R., Fan, L., Wilce, P.A. and Jaquet, V. (2012) MALAT-1, a non protein-coding RNA is upregulated in the cerebellum, hippocampus and brain stem of human alcoholics. Alcohol, 46, 629-634.
- Tian, Y., Zhang, X., Hao, Y., Fang, Z. and He, Y. (2014) Potential roles of abnormally expressed long noncoding RNA UCA1 and Malat-1 in metastasis of melanoma. Melanoma Res.
- Li, Z., Li, C., Liu, C., Yu, S. and Zhang, Y. (2014) Expression of the long non-coding RNAs MEG3, HOTAIR, and MALAT-1 in non-functioning pituitary adenomas and their relationship to tumor behavior. Pituitary.
- Guo, F., Li, Y., Liu, Y., Wang, J. and Li, G. (2010) Inhibition of metastasis-associated lung adenocarcinoma transcript 1 in CaSki human cervical cancer cells suppresses cell proliferation and invasion. Acta Biochim Biophys Sin (Shanghai), 42, 224-229.
- Zhao, Z., Chen, C., Liu, Y. and Wu, C. (2014) 17beta-Estradiol treatment inhibits breast cell proliferation, migration and invasion by decreasing MALAT-1 RNA level. Biochem Biophys Res Commun, 445, 388-393.
- Jeffers, L.K., Duan, K., Ellies, L.G., Seaman, W.T., Burger-Calderon, R.A., Diatchenko, L.B. and Webster-Cyriaque, J. (2013) Correlation of transcription of MALAT-1, a novel noncoding RNA, with deregulated expression of tumor suppressor p53 in small DNA tumor virus models. J Cancer Ther, 4.
- Koshimizu, T.A., Fujiwara, Y., Sakai, N., Shibata, K. and Tsuchiya, H. (2010) Oxytocin stimulates expression of a noncoding RNA tumor marker in a human neuroblastoma cell line. Life Sci, 86, 455-460.
- Schmidt, L.H., Spieker, T., Koschmieder, S., Schaffers, S., Humberg, J., Jungen, D., Bulk, E., Hascher, A., Wittmer, D., Marra, A. et al. (2011) The long noncoding MALAT-1 RNA indicates a poor prognosis in non-small cell lung cancer and induces migration and tumor growth. J Thorac Oncol, 6, 1984-1992.
- Yamada, K., Kano, J., Tsunoda, H., Yoshikawa, H., Okubo, C., Ishiyama, T. and Noguchi, M. (2006) Phenotypic characterization of endometrial stromal sarcoma of the uterus. Cancer Sci, 97, 106-112.
- Lai, M.C., Yang, Z., Zhou, L., Zhu, Q.Q., Xie, H.Y., Zhang, F., Wu, L.M., Chen, L.M. and Zheng, S.S. (2011) Long non-coding RNA MALAT-1 overexpression predicts tumor recurrence of hepatocellular carcinoma after liver transplantation. Med Oncol, 29, 1810-1816.
- Guffanti, A., Iacono, M., Pelucchi, P., Kim, N., Solda, G., Croft, L.J., Taft, R.J., Rizzi, E., Askarian-Amiri, M., Bonnal, R.J. et al. (2009) A transcriptional sketch of a primary human breast cancer by 454 deep sequencing. BMC Genomics, 10, 163.