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A report reveals that PIAS1 confers DNA-binding specificity on the Msx1homeoprotein by regulating its subnuclear localization and proximity to target genes. It is shown that PIAS1 is required for the appropriate localization and retention of Msx1 at the nuclear periphery in myoblast cells.

A large portion of the eukaryotic genome is transcribed as noncoding RNAs (ncRNAs), which play a central role in regulating gene expression at multiple levels. An overview of recent advances in the identification and function of eukaryotic ncRNAs in chromatin organization, gene expression, and disease etiology is presented.

Genome-wide analyses have identified thousands of long noncoding RNAs (lncRNAs). Malat1 (metastasisassociated 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-PyMTand 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. [ABSTRACT FROM AUTHOR]