MALAT1 — a paradigm for long noncoding RNA function in cancer
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The metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a bona fide long noncoding RNA (lncRNA). MALAT1, also known as nuclear-enriched transcript 2 (NEAT2), was discovered as a prognostic marker for lung cancer metastasis but also has been linked to several other human tumor entities. Recent work established a critical regulatory function of this lncRNA in lung cancer metastasis and cell migration. Moreover, MALAT1 is an interesting target for antimetastatic therapy in non-small cell lung carcinoma. Two alternative modes of action have been proposed for MALAT1: regulation of gene expression or alternative splicing. Although the exact mechanism of action in different physiological and pathological conditions still needs to be elucidated, MALAT1 acts as a regulator of gene expression. Although MALAT1 is highly evolutionary conserved in mammals and plays an important role in cancer and metastasis, MALAT1 is not essential for development in a knockout mouse model under normal physiological conditions. Hence, one central question for the future is finding the right stressor and the pathological or environmental condition which requires MALAT1 expression in vivo and entailing its strong evolutionary conservation. Here, we summarize the current knowledge about this important lncRNA. We introduce its discovery, biogenesis, and regulation and describe its known functions, mechanisms of action, and interaction partners.
KeywordsCancer Metastasis Noncoding RNA ncRNA Gene regulation Gene therapy
We apologize to all scientists whose important work could not be cited in this review due to space constraints. Our research is supported by the German Research Foundation (DFG Transregio TRR77, TP B03), the Marie Curie Program of the European Commission, the Helmholtz Society (VH-NG-504), the Virtual Helmholtz Institute for Resistance in Leukemia, the German Cancer Research Center (DKFZ), and the Institute of Pathology, University of Heidelberg.
Conflict of interest
The authors declare no conflict of interests.
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