Downregulation of KIF15 inhibits the tumorigenesis of non-small-cell lung cancer via inactivating Raf/MEK/ERK signaling

• Yingbin Luo ^[1] ; Bo Zhang ^[1] ; Lili Xu ^[1] ; Minghua Li ^[1] ; Jianchun Wu ^[1] ; Yiyang Zhou ^[1] ; Yan Li ^[1]
  1. [1] Shanghai University of Traditional Chinese Medicine

     Shanghai University of Traditional Chinese Medicine

     China

     
• Localización: Histology and histopathology: cellular and molecular biology, ISSN-e 1699-5848, ISSN 0213-3911, Vol. 37, Nº. 3, 2022, págs. 269-285
• Idioma: inglés
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• Resumen

  • Background. Lung cancer is one of the most common causes of cancer-associated mortality worldwide. Upregulation of kinesin family member 15 (KIF15) expression has been observed in non-small cell lung cancer (NSCLC), and high expression levels of KIF15 are associated with a poor prognosis in patients with NSCLC. However, to the best of our knowledge, the mechanisms by which KIF15 regulates apoptosis, migration and invasion in NSCLC remain unclear.

    Methods. Cell Counting Kit-8, flow cytometry and Transwell assays were performed to determine the proliferation, apoptosis and invasion of NSCLC cells, respectively. In addition, western blotting was used to detect the levels of phosphorylated (p-)c-Raf, p-ERK and p-MEK in NSCLC cells.

    Results. Downregulation of KIF15 expression markedly inhibited the proliferation, migration and invasion of NSCLC cells through mediation of MMP2 and MMP9. In addition, downregulation of KIF15 markedly induced apoptosis and cell cycle arrest in NSCLC cells through regulation of active caspase 3, p27 Kip1 and cyclin D1. Furthermore, KIF15 knockdown notably decreased the levels of activating transcription factor 2, p-c-Raf, p-ERK and p-MEK in A549 and NCIH460 cells. Finally, KIF15 knockdown notably inhibited the tumor growth of NSCLC in vivo.

    Conclusion. In conclusion, the present study indicated that downregulation of KIF15 expression was able to inhibit the tumorigenesis of NSCLC by inactivating Raf/MEK/ERK signaling. These findings may help improve the diagnosis and treatment of NSCLC.