English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Tools annual

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Presents the access of premium content as premium feature

Premium Content

Global: Zendy Plus annual

Global: Zendy Free Plan

Our previous studies have reported that RFPL3 protein exerts its unique function as a transcriptional factor of hTERT promoter after being transported into the lung cancer cell nucleus. However, the detailed mechanism by which RFPL3 undergoes nuclear transport has not been reported yet. Here, we identified RFPL3 as a potential import cargo for IPO13, which was found to be overexpressed in NSCLC cells and tissues. IPO13 interacted with RFPL3 in lung cancer cells, and the knockdown of IPO13 led to the cytoplasmic accumulation of RFPL3, the decreased anchoring of RFPL3 at hTERT promoter, and the downregulation of hTERT expression. Moreover, IPO13 silencing suppressed tumor growth in vitro and in vivo. IHC analysis confirmed the positive correlation between the expression levels of IPO13 and hTERT in the tumor tissues from patients with lung cancer. Furthermore, the mechanistic study revealed that IPO13 recognized RFPL3 via a functional nuclear localization signal (NLS), which is located in the B30.2 domain at the C-terminal region of RFPL3. Of note, the presence of EGFR mutations was significantly related to the increased IPO13 expression. The EGFR-TKI Osimertinib downregulated IPO13 expression level in NSCLC cell lines with EGFR mutations, but not in EGFR wild-type ones. In summary, our data suggest that inhibition of IPO13 transport activity itself might be an alternative and potential therapeutic strategy for NSCLC.

Importin 13 promotes NSCLC progression by mediating RFPL3 nuclear translocation and hTERT expression upregulation