4.6 Article

YAP1 inhibits circRNA-000425 expression and thus promotes oncogenic activities of miR-17 and miR-106

Journal

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 503, Issue 4, Pages 2370-2375

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2018.06.163

Keywords

circRNA-000425; YAP1; miR-17; miR-106; Cancer development

Funding

  1. National Natural Science Foundation of China [81760432, 81660402, 81660405]
  2. JiangXi Province General Project [20164BCD40097, 20171BBG70121, 2017BBH80027]
  3. Youth Scientific Funds-Youth Fund Project [20171BAB215041]
  4. JiangXi Province Education Fund Project [700653002]
  5. department of health of JiangXi Province Project [20181041]

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YAP1, a vital effector of Hippo pathway, promotes cancer development via transcriptionally regulating a batch of target genes involved in various signaling pathways, including proliferation, apoptosis, and cell drug sensitivity. Recently, circular RNAs (circRNAs) have been shown to control gene expression post transcriptionally and become a new layer of gene regulation. However, whether circRNAs play roles in YAP1-induced tumorigenesis is still largely elusive. Here, we identify circRNA-000425 as a new inhibitory target of YAP1, and also find that it binds to miR-17/miR-106b, and thus suppresses cancer cell growth induced by these miRNAs. circRNA-000425 is revealed as a YAP1 target through circRNA microarray analysis of RNAs extracted from cells treated with or without YAP1 siRNAs, and further confirmed by RT-q-PCR and ChIP assays. Interestingly, bioinformatics analysis, luciferase assay, and RT-q-PCR results showed that circRNA-000425 binds to miR-17 and miR-106b, but not let-7a, and rescues the inhibitory effect of miR-17/miR-106 on the expressions of both p21 and BIM. In addition, colony formation and MTT assay showed that circRNA-000425 inhibits cancer cell growth induced by miR-17. These findings reveal a mechanism by which YAP1 promotes oncogenic activities of miR-17 and miR-106b through transcriptionally inhibiting circRNA-000425 expression. (C) 2018 Elsevier Inc. All rights reserved.

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