Long non-coding RNA SNHG1 contributes to cisplatin resistance in non-small cell lung cancer by regulating miR-140-5p/Wnt/β-catenin pathway

Neoplasma. 2019 Sep;66(5):756-765. doi: 10.4149/neo_2018_181218N980. Epub 2019 Jun 18.

Abstract

Small nucleolar RNA host gene 1 (SNHG1) has been identified to function as an oncogene in a large number of human cancers. Nevertheless, the biologic role and underlying molecular mechanism of SNHG1 on cisplatin (DDP)-resistance in NSCLC is still unknown. qRT-PCR assay was performed to assess the expression levels of SNHG1 and miR-140-5p. Western blot analysis was used to determine Wnt1, cyclinD1, c-Myc and β-catenin levels. The direct correlation between SNHG1 and miR-140-5p was verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. CCK-8 assay and Transwell assay were applied to determine cell proliferation ability, and cell migration and invasion capacities, respectively. Tumor xenograft was performed to confirm the effect of SNHG1 on DDP-resistance of NSCLC in vivo. Our data showed SNHG1 was upregulated in DDP-resistant NSCLC tissues and cell lines. SNHG1 knockdown suppressed the proliferation, migration, invasion and DDP-resistance in DDP-resistant NSCLC cell lines in vitro and inhibited tumor growth in vivo. Moreover, SNHG1 repressed miR-140-5p expression by directly binding to miR-140-5p. SNHG1-knockdown-mediated regulatory effect was antagonized by miR-140-5p. Furthermore, Wnt/β-catenin signaling was involved in SNHG1/miR-140-5p-mediated regulation in DDP-resistance of NSCLC cell lines. The results suggested that SNHG1 knockdown ameliorated DDP-resistance of NSCLC by regulating miR-140-5p/Wnt/β-catenin pathway, providing a new potential therapeutic target for DDP-resistance NSCLC treatment.

MeSH terms

  • Animals
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Cell Line, Tumor
  • Cisplatin
  • Drug Resistance, Neoplasm*
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • Lung Neoplasms / drug therapy*
  • Mice
  • MicroRNAs / genetics*
  • RNA, Long Noncoding / genetics*
  • Wnt Signaling Pathway*
  • Xenograft Model Antitumor Assays

Substances

  • MicroRNAs
  • Mirn140 microRNA, human
  • RNA, Long Noncoding
  • long non-coding RNA SNHG1, human
  • Cisplatin