Reference - Detail
|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.|
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.
|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|
|DNA material||CSII-CMV-MCS-IRES2-Bsd (RDB07082) CSII-EF-MCS-IRES2-Venus (RDB04384)|