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

Abstract

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:

• lncRNA
• BLACAT1
• afatinib resistance
• STAT3
• lung cancer

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Disclosure statement

The authors have no conflicts of interest to declare.

Additional information

Funding

This study was supported by a grant from the Natural Science Foundation of Zhejiang province [No. LQ20H160057], the Key Discipline of Jiaxing Respiratory Medicine Construction Project [No. 2019-zc-04], the Early Diagnosis and Comprehensive Treatment of Lung Cancer Innovation Team Building Project, Zhejiang North Regional Anaesthesia Special Disease Center, Clinical Research Project in Medical Committee of Zhejiang Province [No. 2013ZYC-A89], Science and technology project of Jiaxing [2019AY32030] and Talent Cultivation in Science and Technology Innovation Project of The First Hospital of Jiaxing [No. 2016-CX-04, 2016-CX-05].