NCK1-AS1 promotes NCK1 expression to facilitate tumorigenesis and chemo-resistance in ovarian cancer

Biochem Biophys Res Commun. 2020 Feb 5;522(2):292-299. doi: 10.1016/j.bbrc.2019.11.014. Epub 2019 Nov 21.


Long non-coding RNAs (lncRNAs) have been unveiled to play crucial parts in tumorigenesis and chemo-resistance of multiple cancers. Herein, we explored the role of NCK1-AS1 in ovarian cancer (OC). As indicated by TCGA, NCK1-AS1 was markedly upregulated in OC tissues. Besides, we found a dramatic upregulation of NCK1-AS1 in OC cell lines relative to the normal IOSE cells. Interestingly, silencing NCK1-AS1 confined cell proliferation, induced apoptosis and suppressed migration and invasion as well as enhanced DDP sensitivity in OC cells. As for mechanistic investigation, starBase ( suggested that NCK1-AS1 expression in OC tissues was significantly positively correlated with its adjacent gene, NCK adaptor protein 1 (NCK1). Furtherly, we demonstrated that the cytoplasmic NCK1-AS1 competed with NCK1 mRNA for miR-137 binding to boost NCK1 mRNA expression. Importantly, miR-137 inhibition could only offset the suppression of NCK1-AS1 depletion on NCK1 mRNA level but not the protein level. Moreover, NCK1-AS1 stabilized NCK1 protein by hindering c-Cbl-induced degradation via directly interacting with c-Cbl. Furthermore, NCK1 upregulation reversed the influences of NCK1-AS1 inhibition on the biological behaviors and DDP resistance of OC cells. This study disclosed a NCK1-AS1/NCK1 axis in regulating OC progression and chemo-resistance, opening a new path for treatment and chemo-resistance overcoming in OC.

Keywords: Chemo-resistance; NCK1; NCK1-AS1; Ovarian cancer.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adaptor Proteins, Signal Transducing / metabolism
  • Base Sequence
  • Carcinogenesis / genetics*
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cisplatin / pharmacology
  • Cisplatin / therapeutic use
  • Disease Progression
  • Drug Resistance, Neoplasm / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Gene Knockdown Techniques
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Neoplasm Invasiveness
  • Oncogene Proteins / genetics*
  • Oncogene Proteins / metabolism
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology
  • Proteolysis
  • Proto-Oncogene Proteins c-cbl / metabolism
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Up-Regulation / genetics


  • Adaptor Proteins, Signal Transducing
  • MIRN137 microRNA, human
  • MicroRNAs
  • Nck protein
  • Oncogene Proteins
  • RNA, Long Noncoding
  • RNA, Messenger
  • Proto-Oncogene Proteins c-cbl
  • Cisplatin