PKNOX2 suppresses lung cancer cell proliferation by inhibiting the PI3K/AKT/mTOR axis

Song,Minglei; Zhang,Nan; Cao,Fumin; Liu,Junfeng

doi:10.3892/etm.2023.11917

PKNOX2 suppresses lung cancer cell proliferation by inhibiting the PI3K/AKT/mTOR axis

Authors:
- Minglei Song
- Nan Zhang
- Fumin Cao
- Junfeng Liu
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Affiliations: Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China
Published online on: March 28, 2023 https://doi.org/10.3892/etm.2023.11917
Article Number: 217
Copyright: © Song et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

PBX/knotted 1 homeobox 2 (PKNOX2) has been implicated in tumorigenesis; however, its role in lung cancer (LC) remains unknown. The present study thus aimed to examine the expression, regulation, function and clinical implication of PKNOX2 in LC. A series of experiments were performed, including Cell Counting Kit‑8 assay, cell cycle analysis, wound‑healing assay, Transwell assay, methylation‑specific PCR and western blotting. Bioinformatics analysis revealed that PKNOX2 was a LC‑related gene, and a decrease in its expression was found in LC tissues from three public datasets. The results of reverse transcription‑quantitative PCR assays also confirmed that PKNOX2 mRNA expression was markedly downregulated in LC tissues (n=60, P<0.01) and in five types of LC cell lines, and this was associated with the promoter methylation of PKNOX2. In addition, PKNOX2 expression was significantly associated with tumor invasion (P<0.0001), lymph node metastasis (P=0.0057) and TNM stage (P=0.0003); however, it was not associated with sex, age, pathological type or distant metastasis. The data obtained in vitro demonstrated that PKNOX2 silencing promoted LC cell proliferation and inhibited cell cycle arrest, accompanied by an increase in the expression levels of cell cycle‑related proteins (cyclinD1, cyclinE1, CDK2 and CDK4), whereas PKNOX2 overexpression exhibited the opposite trend. In addition, PKNOX2 inhibited the migration and invasion of LC cells. Mechanistically, PKNOX2 knockdown activated the PI3K/AKT/mTOR signaling pathway by accelerating the phosphorylation of PI3K, AKT and mTOR, whereas PKNOX2 overexpression inactivated this signaling pathway. In conclusion, the findings of the present study suggested that PKNOX2 may suppress LC cell proliferation by inhibiting the PI3K/AKT/mTOR axis.

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