CDKL3 Promotes Non-small Cell Lung Cancer by Suppressing Autophagy Via Activation of PI3K/Akt/mTOR Pathway

This study aimed to assess the role of cyclin-dependent kinase-like 3 (CDKL3) in the progression of non-small cell lung cancer (NSCLC) as well as the underlying mechanisms. Western blot and qRT-PCR were utilized to analyze CDKL3 expression in 30 pairs of NSCLC and paraneoplastic tissues. A549 cells with CDKL3 knockdown and PC9 cells with CDKL3 overexpression were constructed by infecting cells with lentiviruses expressing shRNA of CDKL3 and expressing a full-length CDKL3 mRNA, respectively. The CCK-8 assay, flow cytometry, wound healing assay, and Transwell assay were carried out to detect cell viability, apoptosis, migration, and invasion, respectively. Autophagosome morphology was observed by electron microscopy experiments, the expression of key components of the PI3K/Akt/mTOR pathway was examined via Western blot and their mRNA expression levels were determined. Besides, the stably infected NSCLC cells with reduced expression or overexpression of CDKL3 were inoculated into the right-back flank of mice to generate tumors. The results showed that CDKL3 expression was dramatically increased in NSCLC tissues. Moreover, CDKL3 promoted the viability and migration of NSCLC cells by suppressing autophagy in vitro and in vivo. In addition, CDKL3 might modulate PI3K/Akt/mTOR signaling in NSCLC. Overall, CDKL3 might promote NSCLC cell viability and metastasis by inhibiting autophagy and activating the PI3K/Akt/mTOR signaling pathway.