MiR-361 targets Yes-associated protein (YAP) mRNA to suppress cell proliferation in lung cancer

Biochem Biophys Res Commun. 2017 Oct 21;492(3):468-473. doi: 10.1016/j.bbrc.2017.08.072. Epub 2017 Aug 21.

Abstract

Yes-associated protein (YAP) contributes to the development of multiple tumors, but the post-transcription modulation of YAP remains unexplored. Here, we present a new regulatory microRNA of YAP, miR-361, which directly targets YAP to inhibit cell proliferation in lung cancer. We used bioinformatics to predict that miR-361 could target 3'-untranslated region (3'UTR) of YAP mRNA. Luciferase reporter gene assays demonstrated that miR-361 could decrease the luciferase activities of 3'UTR vector of YAP. Furthermore, YAP expression was obviously abated by miR-361 using RT-PCR and immunoblotting in lung cancer A549 cells. In terms of function, MTT and colony formation analysis showed that ectopic miR-361 expression significantly suppressed cell proliferation in lung cancer. Notably, overexpressed YAP accelerated miR-361-bated proliferation of lung cancer cells. MiR-361 inhibitor promoted cell proliferation in lung cancer, but YAP RNA interference reversed miR-361 inhibitor-driven cell proliferation. Interestingly, miR-361 was capable of affecting the cell cycle in lung cancer progression. Finally, the negative correlation of miR-361 with YAP was found in clinical human lung cancer tissues. In conclusion, miR-361 targets 3'UTR of YAP mRNA to depress the proliferation of lung cancer cells.

Keywords: Lung cancer; Proliferation; YAP; miR-361.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Adaptor Proteins, Signal Transducing / genetics*
  • Adaptor Proteins, Signal Transducing / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / genetics*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology*
  • MicroRNAs / genetics*
  • Phosphoproteins / genetics*
  • Phosphoproteins / metabolism
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism
  • Structure-Activity Relationship
  • Transcription Factors
  • YAP-Signaling Proteins

Substances

  • 3' Untranslated Regions
  • Adaptor Proteins, Signal Transducing
  • MIRN361 microRNA, human
  • MicroRNAs
  • Phosphoproteins
  • RNA, Messenger
  • Transcription Factors
  • YAP-Signaling Proteins
  • YAP1 protein, human