Circular RNA circRILPL1 promotes nasopharyngeal carcinoma malignant progression by activating the Hippo-YAP signaling pathway

Cell Death Differ. 2023 Jul;30(7):1679-1694. doi: 10.1038/s41418-023-01171-8. Epub 2023 May 12.

Abstract

Circular RNAs (circRNAs) play an important regulatory role in the pathogenesis and progression of nasopharyngeal carcinoma (NPC), which have not been thoroughly elucidated. In this study, we revealed for the first time that circRILPL1 was upregulated in NPC, weakened adhesion and decreased stiffness of NPC cells, and promoted NPC proliferation and metastasis in vitro and in vivo. Mechanistically, circRILPL1 inhibited the LATS1-YAP kinase cascade by binding to and activating ROCK1, resulting in decrease of YAP phosphorylation. Binding and cooperating with transport receptor IPO7, circRILPL1 promoted the translocation of YAP from the cytoplasm to the nucleus, where YAP enhanced the transcription of cytoskeleton remodeling genes CAPN2 and PXN. By which, circRILPL1 contributed to the pathogenesis of NPC. Our results demonstrated that circRILPL1 promoted the proliferation and metastasis of NPC through activating the Hippo-YAP signaling pathway by binding to both ROCK1 and IPO7. Highly expressed circRILPL1 in NPC may serve as an important biomarker for tumor diagnosis and may also be a potential therapeutic target.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic
  • Hippo Signaling Pathway
  • Humans
  • Nasopharyngeal Carcinoma / genetics
  • Nasopharyngeal Carcinoma / metabolism
  • Nasopharyngeal Neoplasms* / metabolism
  • RNA, Circular* / genetics
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • rho-Associated Kinases / genetics

Substances

  • RNA, Circular
  • Transcription Factors
  • ROCK1 protein, human
  • rho-Associated Kinases