Knockdown of HuR represses osteosarcoma cells migration, invasion and stemness through inhibition of YAP activation and increases susceptibility to chemotherapeutic agents

Biomed Pharmacother. 2018 Jun:102:587-593. doi: 10.1016/j.biopha.2018.03.098. Epub 2018 Apr 5.

Abstract

This study aims to explore the roles and related mechanisms of HuR in osteosarcoma (OS) cells migration, invasion, stemness and chemotherapeutical sensitivity. Here, we found that HuR exhibited higher level in OS tissues compared with the adjacent normal tissues. Knockdown of HuR with lentivirus infection suppressed OS cells migration and invasion, and thus the epithelial-mesenchymal transition (EMT) process. Additionally, HuR knockdown inhibited OS cells stemness. Mechanistically, YAP was identified as a direct target of HuR in OS cells, and HuR knockdown decreased its expression. Moreover, YAP transcriptional activity was attenuated by HuR knockdown, and RNA immunization co-precipitation (RIP) assay showed that HuR directly bound with YAP. Importantly, YAP overexpression rescued the inhibition of HuR knockdown on OS cells migration, invasion and stemness. Furthermore, HuR knockdown enhanced adriamycin sensitivity in OS cells, this effect was attenuated by YAP overexpression too. Importantly, HuR and YAP expression was positively correlated in OS tissues. Therefore, HuR acts as a tumor promoter by enhancing YAP expression in OS cells.

Keywords: Adriamycin; Epithelial-mesenchymal transition; HuR; Osteosarcoma; YAP.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Adult
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Cell Line, Tumor
  • Cell Movement* / drug effects
  • Disease Progression
  • Doxorubicin / pharmacology
  • ELAV-Like Protein 1 / genetics
  • ELAV-Like Protein 1 / metabolism*
  • Epithelial-Mesenchymal Transition
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques*
  • HEK293 Cells
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology*
  • Osteosarcoma / drug therapy*
  • Osteosarcoma / genetics
  • Osteosarcoma / metabolism
  • Osteosarcoma / pathology*
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Protein Binding
  • Transcription Factors
  • Transcription, Genetic
  • YAP-Signaling Proteins

Substances

  • Adaptor Proteins, Signal Transducing
  • Antineoplastic Agents
  • ELAV-Like Protein 1
  • Phosphoproteins
  • Transcription Factors
  • YAP-Signaling Proteins
  • YAP1 protein, human
  • Doxorubicin