KPNA2 promotes renal cell carcinoma proliferation and metastasis via NPM

J Cell Mol Med. 2021 Oct;25(19):9255-9267. doi: 10.1111/jcmm.16846. Epub 2021 Sep 1.

Abstract

Karyopherin α2 (KPNA2), involved in nucleocytoplasmic transport, has been reported to be up-regulated in tumorigenesis. However, comprehensive studies of KPNA2 functions in renal cell carcinoma (RCC) are still lacking. In this study, we aim to investigate the roles of KPNA2 in kidney tumour development. Our results showed that down-regulation of KPNA2 inhibited the proliferation and invasion of kidney tumour cell cells in vitro, while the cell cycle arrest and cellular apoptosis were induced once KPNA2 was silenced. Repression of KPNA2 was proved to be efficient to repress tumorigenesis and development of kidney tumour in in nude mice. Furthermore, one related participator, NPM, was identified based on Co-IP/MS and bioinformatics analyses. The up-regulation of NPM attenuates the efficiency of knockdown KPNA2. These results indicated that KPNA2 may regulate NPM to play a crucial role for kidney tumour development.

Keywords: KPNA2; NPM; kidney renal clear cell carcinoma; proliferation; tumorigenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Carcinoma, Renal Cell / genetics*
  • Carcinoma, Renal Cell / metabolism*
  • Carcinoma, Renal Cell / pathology
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Disease Models, Animal
  • Female
  • Gene Knockdown Techniques
  • Heterografts
  • Humans
  • Kidney Neoplasms / genetics*
  • Kidney Neoplasms / metabolism*
  • Kidney Neoplasms / pathology
  • Mice
  • Nucleophosmin / genetics
  • Nucleophosmin / metabolism*
  • Protein Binding
  • alpha Karyopherins / genetics*
  • alpha Karyopherins / metabolism*

Substances

  • KPNA2 protein, human
  • alpha Karyopherins
  • Nucleophosmin