Differentiation of mammary tumors and reduction in metastasis upon Malat1 lncRNA loss

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…

• ÉN
  École Normale Supérieure
• MU
  McGill University
• IP
  Ionis Pharmaceuticals
• NC
  National Cancer Institute

  Awards: 2P3OCA45508, 5P01CA013106-Project 3, 5P01CA013106