YAP1-induced MALAT1 promotes epithelial-mesenchymal transition and angiogenesis by sponging miR-126-5p in colorectal cancer

Oncogene. 2019 Apr;38(14):2627-2644. doi: 10.1038/s41388-018-0628-y. Epub 2018 Dec 10.

Abstract

Yes-associated protein 1 (YAP1) exerts significant effects in various malignancies. However, the oncogenic role of YAP1 remains controversial, and the mechanism by which YAP1 regulates non-coding RNAs is still largely unknown. The present study aimed to assess the effect of YAP1 on the malignant behaviors of colorectal carcinoma (CRC) and explore the underlying regulatory mechanism of the YAP1-MALAT1-miR-126-5p axis. YAP1 was highly expressed in CRC tissues as assessed by GSE20916 and its expression was negatively correlated with overall survival in 83 CRC cases. Meanwhile, YAP1 promoted proliferation, invasion, and migration in colon cancer cells, in vitro and in vivo. MALAT1 was obviously expressed, with differential expression of 11 lncRNAs in HCT116 cells after transfection with siYAP1 or si-Ctl. Based on bioinformatics prediction, immunoprecipitation (IP), and chromatin immunoprecipitation (ChIP), the interaction of YAP1 with TCF4/β-catenin was regulated by MALAT1. Bioinformatics prediction, dual luciferase assay, RNA-IP, and RNA pull-down assay demonstrated that YAP1-induced MALAT1 promoted the expression of metastasis-associated molecules such as VEGFA, SLUG, and TWIST, by sponging miR-126-5p in CRC. These findings indicated that the YAP1-MALAT1-miR-126-5p axis could control angiogenesis and epithelial-mesenchymal transition in CRC, providing potential biomarkers and therapeutic targets for CRC.

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Caco-2 Cells
  • Cell Line
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • Epithelial-Mesenchymal Transition / genetics*
  • Epithelial-Mesenchymal Transition / physiology
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • HCT116 Cells
  • HEK293 Cells
  • HT29 Cells
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Neovascularization, Pathologic / genetics*
  • Neovascularization, Pathologic / pathology
  • Phosphoproteins / genetics*
  • RNA, Long Noncoding / genetics*
  • Transcription Factors
  • Transcription, Genetic / genetics
  • YAP-Signaling Proteins
  • Young Adult

Substances

  • Adaptor Proteins, Signal Transducing
  • MALAT1 long non-coding RNA, human
  • MIRN126 microRNA, human
  • MicroRNAs
  • Phosphoproteins
  • RNA, Long Noncoding
  • Transcription Factors
  • YAP-Signaling Proteins
  • YAP1 protein, human