Long non‑coding RNA LUCAT1 contributes to cisplatin resistance by regulating the miR‑514a‑3p/ULK1 axis in human non‑small cell lung cancer

Int J Oncol. 2020 Oct;57(4):967-979. doi: 10.3892/ijo.2020.5106. Epub 2020 Aug 7.


Drug resistance is a major obstacle in the therapy of malignant tumors, including non‑small cell lung cancer (NSCLC). Long non‑coding RNAs (lncRNAs) have been demonstrated to be involved in chemoresistance. The present study aimed to investigate the role of lung cancer‑associated transcript 1 (LUCAT1) in cisplatin (DDP) resistance in NSCLC. By using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR), it was found that the expression of LUCAT1 was elevated and that of microRNA‑514a‑3p (miR‑514a‑3p) was decreased in DDP‑resistant NSCLC tissues and cells. Functionally, LUCAT1 upregulation enhanced cisplatin resistance by promoting the viability, autophagy and metastasis, and inhibiting the apoptosis of NSCLC cells, as demonstrated by Cell Counting kit‑8 (CCK‑8) assay, western blot analysis, Transwell assay and flow cytometric analysis. LUCAT1 was identified as a sponge of miR‑514a‑3p and uncoordinated‑51‑like kinase 1 (ULK1) was proven to be a target gene of miR‑514a‑3p by bioinformatics analysis, dual‑luciferase reporter assay and RNA immunoprecipitation (RIP) assay. The enhancing effect of miR‑514a‑3p on cisplatin sensitivity was reversed by the elevation of LUCAT1. ULK1 knockdown suppressed cisplatin resistance, while this effect was attenuated by miR‑514a‑3p inhibition. Moreover, LUCAT1 positively regulated ULK1 expression by targeting miR‑514a‑3p. In addition, LUCAT1 knockdown suppressed tumor growth in vivo. On the whole, the findings of the present study demonstrate that LUCAT1 contributes to the resistance of NSCLC cells to cisplatin by regulating the miR‑514a‑3p/ULK1 axis, elucidating a novel regulatory network in cisplatin resistance in NSCLC.

Keywords: non-small cell lung cancer; LUCAT1; miR-514a-3p; ULK1; cisplatin resistance.

MeSH terms

  • Aged
  • Animals
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Autophagy / drug effects
  • Autophagy-Related Protein-1 Homolog / metabolism*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cisplatin / pharmacology*
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Intracellular Signaling Peptides and Proteins / agonists
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Male
  • Mice
  • Mice, Nude
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Signal Transduction
  • Up-Regulation
  • Xenograft Model Antitumor Assays


  • Antineoplastic Agents
  • Intracellular Signaling Peptides and Proteins
  • MIRN514 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • long non-coding RNA LUCAT1, human
  • Autophagy-Related Protein-1 Homolog
  • ULK1 protein, human
  • Cisplatin