Authors' Affiliations: Division of Molecular Carcinogenesis, Center for Neurological Diseases and Cancer, Department of Cancer Genetics, Program in Function Construction Medicine, and Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine; Division of Molecular Oncology, Aichi Cancer Center Research Institute; Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital; and Institute for Advanced Research, Nagoya University, Nagoya, Japan.
Cancer Res. 2011 Oct 1; 71(19):6165-6173. Epub 2011 Aug 19.
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.
PMID: 21856745 [PubMed - as supplied by publisher] Source: National Library of Medicine.
