Arun, G., Diermeier, S., Akerman, M., Chang, K. C., Wilkinson, J. E., Hearn, S., Kim, Y., MacLeod, A. R., Krainer, A. R., Norton, L., Brogi, E., Egeblad, M., Spector, D. L. (January 2016) Differentiation of mammary tumors and reduction in metastasis upon Malat1 lncRNA loss. Genes Dev, 30 (1). pp. 34-51. ISSN 1549-5477 (Electronic)0890-9369 (Linking) (Public Dataset)
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Abstract
Genome-wide analyses have identified thousands of long noncoding RNAs (lncRNAs). Malat1 (metastasis-associated lung adenocarcinoma transcript 1) is among the most abundant lncRNAs whose expression is altered in numerous cancers. Here we report that genetic loss or systemic knockdown of Malat1 using antisense oligonucleotides (ASOs) in the MMTV (mouse mammary tumor virus)-PyMT mouse mammary carcinoma model results in slower tumor growth accompanied by significant differentiation into cystic tumors and a reduction in metastasis. Furthermore, Malat1 loss results in a reduction of branching morphogenesis in MMTV-PyMT- and Her2/neu-amplified tumor organoids, increased cell adhesion, and loss of migration. At the molecular level, Malat1 knockdown results in alterations in gene expression and changes in splicing patterns of genes involved in differentiation and protumorigenic signaling pathways. Together, these data demonstrate for the first time a functional role of Malat1 in regulating critical processes in mammary cancer pathogenesis. Thus, Malat1 represents an exciting therapeutic target, and Malat1 ASOs represent a potential therapy for inhibiting breast cancer progression.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | Malat1 antisense therapy breast cancer metastasis noncoding RNA tumor differentiation tumor organoids |
| Subjects: | diseases & disorders > cancer > cancer types > breast cancer bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > long non-coding RNA diseases & disorders > cancer > metastasis |
| CSHL Authors: | |
| Communities: | CSHL Cancer Center Program > Gene Regulation and Cell Proliferation CSHL Cancer Center Program > Signal Transduction CSHL labs > Egeblad lab CSHL labs > Krainer lab CSHL labs > Spector lab CSHL Cancer Center Program > Cellular Communication in Cancer Program CSHL Cancer Center Program > Gene Regulation and Inheritance Program |
| Highlight: | Spector, David L. |
| Depositing User: | Matt Covey |
| Date: | 1 January 2016 |
| Date Deposited: | 05 Jan 2016 20:34 |
| Last Modified: | 26 Oct 2020 15:46 |
| PMCID: | PMC4701977 |
| Related URLs: | |
| Dataset ID: | |
| URI: | https://repository.cshl.edu/id/eprint/32206 |
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