期刊
RNA BIOLOGY
卷 9, 期 8, 页码 1076-1087出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/rna.21089
关键词
long non-coding RNA; MALAT1; human knockout model; knockout mouse
资金
- German Research Foundation (DFG) [Transregio TRR77, TP B03]
- Marie Curie Program of the European Commission
- Helmholtz Society [VH-NG-504]
- Virtual Helmholtz Institute for Resistance in Leukemia
- German Cancer Research Center (DKFZ)
- Institute of Pathology, University of Heidelberg
- DKFZ PhD Fellowship
- Graduiertenkolleg [1172]
- German Federal Ministry of Health (BMG)
- Ministry of Higher Education, Research and the Arts of the state of Hessen (HMWK)
- LOEWE Center for Cell
- Gene Therapy Frankfurt [HMWK III L 4-518/17.004 (2010)]
- LOEWE initiative Oncogenic Signaling Frankfurt [HMWK III L 4-518/55.004 (2009)]
The metastasis-associated lung adenocarcinoma transcript 1, MALAT1, is a long non-coding RNA (lncRNA) that has been discovered as a marker for lung cancer metastasis. It is highly abundant, its expression is strongly regulated in many tumor entities including lung adenocarcinoma and hepatocellular carcinoma as well as physiological processes, and it is associated with many RNA binding proteins and highly conserved throughout evolution. The nuclear transcript MALAT-1 has been functionally associated with gene regulation and alternative splicing and its regulation has been shown to impact proliferation, apoptosis, migration and invasion. Here, we have developed a human and a mouse knockout system to study the loss-of-function phenotypes of this important ncRNA. In human tumor cells, MALAT1 expression was abrogated using Zinc Finger Nucleases. Unexpectedly, the quantitative loss of MALAT1 did neither affect proliferation nor cell cycle progression nor nuclear architecture in human lung or liver cancer cells. Moreover, genetic loss of Malat1 in a knockout mouse model did not give rise to any obvious phenotype or histological abnormalities in Malat1-null compared with wild-type animals. Thus, loss of the abundant nuclear long ncRNA MALAT1 is compatible with cell viability and normal development.
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