Linc00173 promotes chemoresistance and progression of small cell lung cancer by sponging miR-218 to regulate Etk expression

Oncogene. 2020 Jan;39(2):293-307. doi: 10.1038/s41388-019-0984-2. Epub 2019 Sep 2.

Abstract

The functional effects of long noncoding RNAs (lncRNAs) in cancer have been widely recognized. However, there is little research on SCLC-related lncRNAs. Here, long intergenic nonprotein coding RNA 173 (Linc00173) was first shown to be involved in chemoresistance and progression of small-cell lung cancer (SCLC). We found that Linc00173 was highly expressed in SCLC chemoresistant cell lines, and promoted SCLC cells chemoresistance, proliferation, and migration-invasion. Animal studies validated that Linc00173 induced tumor chemoresistance and growth of SCLC in vivo. Moreover, Linc00173 upregulated Etk through functioning as a competitive endogenous RNA (ceRNA) by "sponging" miRNA-218 and led to the upregulation of GSKIP and NDRG1, resulting in the translocation of β-catenin. Importantly, expression analysis revealed that both Linc00173 and Etk were upregulated in SCLC patient samples and exhibiting positive Linc00173/Etk correlation. High expression of Linc00173 closely correlated with chemoresistance, extensive stage, and shorter survival in SCLC patients. Collectively, our study illustrated a Linc00173-mediated process that facilitated chemoresistance and progression in SCLC, which might provide treatment strategy against SCLC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cell Cycle Proteins / genetics
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cisplatin / pharmacology
  • Disease Progression
  • Disease-Free Survival
  • Doxorubicin / pharmacology
  • Drug Resistance, Neoplasm / genetics
  • Etoposide / pharmacology
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Protein-Tyrosine Kinases / genetics*
  • RNA, Long Noncoding / genetics*
  • Repressor Proteins / genetics
  • Small Cell Lung Carcinoma / drug therapy*
  • Small Cell Lung Carcinoma / genetics
  • Small Cell Lung Carcinoma / pathology
  • beta Catenin / genetics

Substances

  • Cell Cycle Proteins
  • GSKIP protein, human
  • Intracellular Signaling Peptides and Proteins
  • MIRN218 microRNA, human
  • MicroRNAs
  • N-myc downstream-regulated gene 1 protein
  • RNA, Long Noncoding
  • Repressor Proteins
  • beta Catenin
  • long noncoding RNA LINC00173, human
  • Etoposide
  • Doxorubicin
  • BMX protein, human
  • Protein-Tyrosine Kinases
  • Cisplatin