马拉特1
生物
基因敲除
癌症研究
转移
乳腺肿瘤
腺癌
癌症
小鼠乳腺肿瘤病毒
长非编码RNA
基因
乳腺癌
遗传学
下调和上调
作者
Gayatri Arun,Sarah Diermeier,Martin Akerman,Kung Chi Chang,John E. Wilkinson,Stephen Hearn,Youngsoo Kim,A. Robert MacLeod,Adrian R. Krainer,Larry Norton,Edi Brogi,Mikala Egeblad,David L. Spector
出处
期刊:Genes & Development
[Cold Spring Harbor Laboratory]
日期:2015-12-23
卷期号:30 (1): 34-51
被引量:452
标识
DOI:10.1101/gad.270959.115
摘要
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.
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