論文 - 詳細
RRC ID | 12769 |
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著者 | 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. |
タイトル | miR-375 is activated by ASH1 and inhibits YAP1 in a lineage-dependent manner in lung cancer. |
ジャーナル | 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. |
巻・号 | 71(19) |
ページ | 6165-73 |
公開日 | 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 Adenocarcinoma of Lung 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 Transcription Factors YAP-Signaling Proteins |
IF | 9.727 |
引用数 | 89 |
WOS 分野 | ONCOLOGY |
リソース情報 | |
遺伝子材料 | CSII-CMV-MCS-IRES2-Bsd (RDB07082) CSII-EF-MCS-IRES2-Venus (RDB04384) |