The long intergenic noncoding RNA GAS5 reduces cisplatin-resistance in non-small cell lung cancer through the miR-217/LHPP axis

Aging (Albany NY). 2021 Jan 8;13(2):2864-2884. doi: 10.18632/aging.202352. Epub 2021 Jan 8.


Long noncoding RNAs (lncRNAs) are known to exert their effects to tumor progression. In this study, the role of the lncRNA GAS5 (growth arrest specific 5) was confirmed in reducing non-small cell lung cancer (NSCLC) cisplatin (DDP) resistance. In NSCLC tissue samples, GAS5 expression decreased significantly. Low GAS5 levels were positively correlated with NSCLC characteristics including TNM, tumor size and lymphatic metastasis. Functionally, GAS5 significantly reduced NSCLC/DDP cell migration, invasion and epithelial-mesenchymal transition (EMT) progression in vitro. In vivo, GAS5 upregulation inhibited remarkably NSCLC/DDP cell tumor growth. Mechanism analysis suggested that GAS5 was a molecular sponge of miR-217, inhibiting the expression of phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP). In conclusion, this study reveals that the GAS5/miR-217/LHPP pathway reduces NSCLC cisplatin resistance and that LHPP may serve as a potential therapeutic target for NSCLC cisplatin resistance.

Keywords: LHPP; miR-217; non-small cell lung cancer.

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cisplatin / therapeutic use*
  • Drug Resistance, Neoplasm / genetics*
  • Epithelial-Mesenchymal Transition / drug effects
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Inorganic Pyrophosphatase / genetics
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Male
  • Mice
  • MicroRNAs / genetics
  • Middle Aged
  • RNA, Long Noncoding / genetics*
  • Signal Transduction / genetics
  • Xenograft Model Antitumor Assays


  • Antineoplastic Agents
  • MIRN217 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • Inorganic Pyrophosphatase
  • phospholysine phosphohistidine inorganic pyrophosphate phosphatase, human
  • Cisplatin