Long non‑coding RNA LINC00473/miR‑195‑5p promotes glioma progression via YAP1‑TEAD1‑Hippo signaling

Int J Oncol. 2020 Feb;56(2):508-521. doi: 10.3892/ijo.2019.4946. Epub 2019 Dec 18.

Abstract

There is an urgent need to identify novel potential therapeutic targets for diagnosis and treatment of glioma, a common primary tumor in brain, due to its high‑level invasiveness. Long non‑coding RNA (lncRNA) LINC00473 has been reported as potentially critical regulators in various types of cancer tumorigenesis. However, the effects of LINC00473 on glioma cells is unclear. The present study aimed to investigate the clinical significance, effects and mechanism of LINC00437 on glioma tumorigenesis. In the present study, LINC00473 was significantly increased in glioma tissues and in cell models, and predicted a poor prognosis in patients with glioma. Notably, LINC00473 knockdown not only suppressed cell proliferation, invasion and migration of glioma cells, but also blocked cell cycle progression and induced apoptosis. Subcutaneous xenotransplanted tumor model experiments revealed that reduced LINC00473 expression was able to suppress in vivo glioma growth. Mechanistically, LINC00473 functioned as a competing endogenous (ce)RNA to decrease microRNA (miR)‑195‑5p expression. Moreover, Yes‑associated protein 1 (YAP1) and TEA domain family member 1 (TEAD1) were identified as downstream targets of miR‑195‑5p, whose expression levels were inhibited by miR‑195‑5p. LINC00473 knockdown suppressed glioma progression through the decrease of miR‑195‑5p and subsequent increase of YAP1 and TEAD1 expression levels. These results indicated LINC00473 might act as a ceRNA to sponge miR‑195‑5p, thus promoting YAP1 and TEAD1 expressions, and shedding light on the underlying mechanisms of LINC00473‑induced glioma progression.

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Adult
  • Aged
  • Apoptosis / genetics
  • Brain / pathology
  • Brain / surgery
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / mortality
  • Brain Neoplasms / pathology
  • Brain Neoplasms / surgery
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • DNA-Binding Proteins / metabolism
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Glioma / genetics*
  • Glioma / mortality
  • Glioma / pathology
  • Glioma / surgery
  • Hippo Signaling Pathway
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • MicroRNAs / metabolism*
  • Middle Aged
  • Nuclear Proteins / metabolism
  • Prognosis
  • Protein Serine-Threonine Kinases / metabolism
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Signal Transduction / genetics*
  • TEA Domain Transcription Factors
  • Transcription Factors / metabolism
  • Xenograft Model Antitumor Assays
  • YAP-Signaling Proteins

Substances

  • Adaptor Proteins, Signal Transducing
  • DNA-Binding Proteins
  • LINC00473 RNA, human
  • MIRN195 microRNA, human
  • MicroRNAs
  • Nuclear Proteins
  • RNA, Long Noncoding
  • TEA Domain Transcription Factors
  • TEAD1 protein, human
  • Transcription Factors
  • YAP-Signaling Proteins
  • YAP1 protein, human
  • Protein Serine-Threonine Kinases