RRC ID 12769
Author Nishikawa E, Osada H, Okazaki Y, Arima C, Tomida S, Tatematsu Y, Taguchi A, Shimada Y, Yanagisawa K, Yatabe Y, Toyokuni S, Sekido Y, Takahashi T.
Title miR-375 is activated by ASH1 and inhibits YAP1 in a lineage-dependent manner in lung cancer.
Journal Cancer Res.
Abstract Lung cancers with neuroendocrine (NE) features are often very aggressive but the underlying molecular mechanisms remain elusive. The transcription factor ASH1/ASCL1 is a master regulator of pulmonary NE cell development that is involved in the pathogenesis of lung cancers with NE features (NE-lung cancers). Here we report the definition of the microRNA miR-375 as a key downstream effector of ASH1 function in NE-lung cancer cells. miR-375 was markedly induced by ASH1 in lung cancer cells where it was sufficient to induce NE differentiation. miR-375 upregulation was a prerequisite for ASH1-mediated induction of NE features. The transcriptional coactivator YAP1 was determined to be a direct target of miR-375. YAP1 showed a negative correlation with miR-375 in a panel of lung cancer cell lines and growth inhibitory activities in NE-lung cancer cells. Our results elucidate an ASH1 effector axis in NE-lung cancers that is functionally pivotal in controlling NE features and the alleviation from YAP1-mediated growth inhibition.
Volume 71(19)
Pages 6165-73
Published 2011-10-1
DOI 10.1158/0008-5472.CAN-11-1020
PII 0008-5472.CAN-11-1020
PMID 21856745
MeSH Adaptor Proteins, Signal Transducing / genetics* Adaptor Proteins, Signal Transducing / metabolism Adenocarcinoma* / genetics Adenocarcinoma* / pathology Basic Helix-Loop-Helix Transcription Factors / genetics* Basic Helix-Loop-Helix Transcription Factors / metabolism Carcinoma, Small Cell* / genetics Carcinoma, Small Cell* / pathology Cell Differentiation Cell Line, Tumor Cell Proliferation Gene Expression Regulation, Neoplastic Humans Lung Neoplasms* / genetics Lung Neoplasms* / pathology MicroRNAs / genetics* MicroRNAs / metabolism Phosphoproteins / genetics* Phosphoproteins / metabolism
IF 8.378
Times Cited 57
DNA material CSII-CMV-MCS-IRES2-Bsd (RDB07082) CSII-EF-MCS-IRES2-Venus (RDB04384)