LncRNA THOR attenuates cisplatin sensitivity of nasopharyngeal carcinoma cells via enhancing cells stemness

Biochimie. 2018 Sep:152:63-72. doi: 10.1016/j.biochi.2018.06.015. Epub 2018 Jun 26.

Abstract

The roles and mechanisms of long non-coding RNAs (lncRNA) in nasopharyngeal carcinoma (NPC) cells stemness and chemotherapeutic sensitivity are unclear. Here, Quantitative real-time PCR (qRT-PCR) was performed to detect the lncRNA THOR expression in NPC and normal adjacent tissues, adherent NPC cells and non-adherent NPC spheres, and we found that THOR was significantly increased in NPC tissues and non-adherent NPC spheres. Further in vitro and in vivo experiments were carried out and identified that knockdown of THOR attenuated NPC cells stemness, characterized as the decrease of spheres formation ability, cell proliferation, migration, invasion, stemness markers expression and tumor initiation, and enhanced cisplatin sensitivity of NPC cells. Mechanistically, RNA immunoprecipitation (RIP), immunofluorescence and luciferase reporter analysis indicated that THOR could enhance YAP transcriptional activity via directly binding to YAP and suppressing its translocation from nuclear to cytoplasm. Notably, overexpression of YAP rescued the inhibition of THOR knockdown on NPC cells and spheres stemness and promotion on cisplatin sensitivity. Thus, our results demonstrate that lncRNA THOR could attenuate cisplatin sensitivity of NPC cells by enhancing cells stemness through promoting YAP transcriptional activity.

Keywords: Carcinoma (NPC); Cisplatin; LncRNA; Nasopharyngeal; Stemness; THOR; YAP.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Adult
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Blotting, Western
  • Carcinoma / metabolism
  • Carcinoma / pathology*
  • Cell Line, Tumor
  • Cisplatin / pharmacology*
  • Gene Knockdown Techniques
  • Humans
  • Immunoprecipitation
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • Middle Aged
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms / metabolism
  • Nasopharyngeal Neoplasms / pathology*
  • Neoplastic Stem Cells / drug effects*
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism
  • Prognosis
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism
  • RNA, Long Noncoding / physiology*
  • Real-Time Polymerase Chain Reaction
  • Transcription Factors
  • Transcription, Genetic
  • YAP-Signaling Proteins

Substances

  • Adaptor Proteins, Signal Transducing
  • Antineoplastic Agents
  • Phosphoproteins
  • RNA, Long Noncoding
  • Transcription Factors
  • YAP-Signaling Proteins
  • YAP1 protein, human
  • Cisplatin