Long noncoding RNA NEAT1 aggravates sorafenib-resistance in non-small cell lung cancer via regulating miRNA-335/c-Met

J BUON. 2021 Mar-Apr;26(2):345-352.


Purpose: The purpose of this study was to illustrate the role of long non-coding RNA (lncRNA) NEAT1 in inhibiting sorafenib sensitivity in non-small cell lung cancer (NSCLC) through targeting microRNA-335 (miR-335)/c-Met axis.

Methods: Regulatory effects of NEAT1/miR-335/c-Met axis on proliferative ability of sorafenib-induced A549 and PC9 cells were assessed by cell counting kit-8 (CCK-8) and colony formation assay. Apoptosis changes influenced by nuclear paraspeckle assembly transcript 1 (NEAT1)/miR-335/c-Met axis after sorafenib treatment in lung cancer cells were examined by detecting apoptotic rate, as well as relative levels of Bcl-2 and Bax. The interaction among NEAT1/miR-335/c-Met was analyzed through dual-luciferase reporter gene assay.

Results: Sorafenib treatment in A549 cells and PC9 cells attenuated the proliferation and induced apoptosis, which were more pronounced after silencing of NEAT1. MiR-335 was the downstream target of NEAT1, and its level was negatively regulated by NEAT1. Moreover, c-Met was the target gene of MiR -335. Rescue experiments verified the role of NEAT1/ MiR-335/c-Met regulatory loop in reducing the proliferative ability and inducing apoptosis of sorafenib-treated lung cancer cells.

Conclusions: LncRNA NEAT1 aggravates sorafenib resistance in NSCLC through inhibiting MiR-335 to upregulate c-Met level, manifesting as attenuated proliferation and accelerated apoptosis.

MeSH terms

  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Drug Resistance, Neoplasm / immunology*
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism
  • MicroRNAs / metabolism*
  • Proto-Oncogene Proteins c-met / metabolism*
  • RNA, Long Noncoding / metabolism*
  • Sorafenib / pharmacology*


  • MIRN335 microRNA, human
  • MicroRNAs
  • NEAT1 long non-coding RNA, human
  • RNA, Long Noncoding
  • Sorafenib
  • Proto-Oncogene Proteins c-met