MiR-375 is activated by ASH1 and inhibits YAP1 in a lineage-dependent manner in lung cancer

Eri Nishikawa, Hirotaka Osada, Yasumasa Okazaki, Chinatsu Arima, Shuta Tomida, Yoshio Tatematsu, Ayumu Taguchi, Yukako Shimada, Kiyoshi Yanagisawa, Yasushi Yatabe, Shinya Toyokuni, Yoshitaka Sekido, Takashi Takahashi

Research output: Contribution to journalArticlepeer-review

97 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)6165-6173
Number of pages9
JournalCancer Research
Volume71
Issue number19
DOIs
Publication statusPublished - Oct 1 2011

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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