miR-375 Is Activated by ASH1 and Inhibits YAP1 in a Lineage-Dependent Manner in Lung Cancer
E Nishikawa, H Osada, Y Okazaki, C Arima, S Tomida… - Cancer research, 2011 - AACR
E Nishikawa, H Osada, Y Okazaki, C Arima, S Tomida, Y Tatematsu, A Taguchi, Y Shimada…
Cancer research, 2011•AACRLung 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 …
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 …
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. Cancer Res; 71(19); 6165–73. ©2011 AACR.
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