LncRNA SNHG1 functions as a ceRNA to antagonize the effect of miR-145a-5p on the down-regulation of NUAK1 in nasopharyngeal carcinoma cell

J Cell Mol Med. 2019 Apr;23(4):2351-2361. doi: 10.1111/jcmm.13497. Epub 2018 Mar 25.

Abstract

How lncRNA SNHG1 influences the aggressiveness of nasopharyngeal carcinoma cells as well as the underlying mechanism was studied. The lncRNA differences were analysed by GSE12452 gene microarray. The expression of SNHG1, MiR-145-5p and NUAK1 was identified by qRT-PCR and western blot. Transfection was conducted to construct nasopharyngeal carcinoma cells with different expressions of SNHG1, miR-145-5p and NUAK1. Dual-luciferase reporter assay was performed to explore the relationship between SNHG1, miR-145-5p and NUAK1. Wound-healing assay and transwell invasion experiments were employed to study changes in cell migration capacity and cell invasion, respectively. Tumour xenografts were performed to observe lung metastasis of nude mice inoculated with transfected CNE cells. SNHG1 is highly expressed in nasopharyngeal carcinoma tissues and in cell lines. Down-regulation of SNHG1 facilitated the expression of miR-145-5p and further suppressed the level of NAUK1 in CNE and HNE-1 cells. Silencing of SNHG1, up-regulation of miR-145-5p and inhibition of NAUK1 by relative transfection all attenuated the aggressiveness of CNE and HNE-1 cells both in vivo and in vitro. Moreover, the impaired cell migration and invasion by SNHG1 siRNA could be rescued by cotransfection of miR-145-5p in CNE and HNE-1 cells. LncRNA SNHG1 promoted the expression of NUAK1 by down-regulating miR-145-5p and thus promoted the aggressiveness of nasopharyngeal carcinoma cells through AKT signalling pathway and induced epithelial-mesenchymal transition (EMT).

Keywords: EMT; NUAK1; SNHG1; miR-145-5p; nasopharyngeal carcinoma.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Epithelial-Mesenchymal Transition / genetics
  • Gene Expression Regulation, Neoplastic / genetics
  • Heterografts
  • Humans
  • Mice
  • MicroRNAs / genetics*
  • Nasopharyngeal Carcinoma / genetics*
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Protein Kinases / genetics*
  • RNA, Long Noncoding / genetics*
  • Repressor Proteins / genetics*

Substances

  • MIRN145 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • Repressor Proteins
  • long non-coding RNA SNHG1, human
  • Protein Kinases
  • NUAK1 protein, human