Knockdown of lncRNA BLACAT1 reverses the resistance of afatinib to non-small cell lung cancer via modulating STAT3 signalling

J Drug Target. 2020 Mar;28(3):300-306. doi: 10.1080/1061186X.2019.1650368. Epub 2019 Aug 5.


Afatinib, a second-generation irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), has been approved as EGFR, HER2, HER3 and HER4 inhibitor for non-small cell lung cancer (NSCLC) treatment. However, acquired resistance to afatinib has been found in most EGFR mutant NSCLC patients. Bladder cancer associated transcript 1 (BLACAT1) is a novel long non-coding RNAs (lncRNA) that play a functional role as an oncogenic lncRNA and is associated with chemoresistance. We aimed to identify the role of BLACAT1 in afatinib-resistant NSCLC and underlying mechanisms. Afatinib-resistant NSCLC cells were established. MTT assay, colony formation assay, apoptosis analysis, qRT-PCR and western blot analysis, immunohistochemistry, and in vivo study were carried out. BLACAT1 was up-regulated in afatinib-resistant NSCLC cells. Knockdown of BLACAT1 reversed the resistance of afatinib to NSCLC cells by modulating STAT3 signalling. The results provided a potential strategy for afatinib-resistant NSCLC by targeting BLACAT1.

Keywords: BLACAT1; STAT3; afatinib resistance; lncRNA; lung cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Afatinib / pharmacology*
  • Animals
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Drug Resistance, Neoplasm / genetics
  • Gene Knockdown Techniques
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Protein Kinase Inhibitors / pharmacology
  • RNA, Long Noncoding / genetics*
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction / drug effects
  • Xenograft Model Antitumor Assays


  • Protein Kinase Inhibitors
  • RNA, Long Noncoding
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • long noncoding RNA BLACAT1, human
  • Afatinib