Targeting Pokemon is a novel strategy to suppress cancer aggressiveness of non-small cell lung cancer: Identification of Pokemon as ideal target for developing anti-NSCLC drugs.

Hao Chang, Wenxue Sun, Yiming Zhao, Tianhao Sun, Zhihong Zhao

Archives of biochemistry and biophysics 2023 Jul 01

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Although it is widely reported that Pokemon acts as an oncogene in the pathogenesis of multiple cancers, but its role and detailed molecular mechanisms in regulating non-small cell lung cancer (NSCLC) progression have not been fully delineated. Here, by performing Real-Time qPCR analysis, we verified that Pokemon was high-expressed in NSCLC tissues and cells, compared to the corresponding normal lung tissues and epithelial cells. Then, the small interfering RNA (siRNA) for Pokemon was transfected into the NSCLC cells to verify its biological functions, and our results suggested that silencing of Pokemon suppressed the malignant phenotypes, including cell viability, mitosis, colony formation, epithelial-mesenchymal transition (EMT), mobility and cancer stem cell (CSC) properties in NSCLC cells. Mechanistically, we confirmed that knockdown of Pokemon decreased the expression levels of phosphorylated Akt (p-Akt), phosphorylated GSK-3β (p-GSK-3β) and Snail to inactivate the oncogenic Akt/GSK-3β/Snail signal pathway, and deletion of Snail also had similar effects to hamper the development of NSCLC. Next, our rescuing experiments validated that Pokemon ablation-induced suppressing effects on NSCLC cell malignancy were all abrogated by overexpressing Snail. Finally, the in vivo experiments confirmed that silencing of Pokemon downregulated Snail to hamper tumorigenesis of NSCLC cells in xenograft tumor-bearing mice models. Taken together, we firstly uncovered the underlying mechanisms by which the Pokemon/Akt/GSK-3β/Snail signal pathway contributed to the development of NSCLC, and this signal pathway could be potentially used as therapeutic targets for the development of personalized anti-NSCLC drugs. Copyright © 2023 Elsevier Inc. All rights reserved.

Citation

Hao Chang, Wenxue Sun, Yiming Zhao, Tianhao Sun, Zhihong Zhao. Targeting Pokemon is a novel strategy to suppress cancer aggressiveness of non-small cell lung cancer: Identification of Pokemon as ideal target for developing anti-NSCLC drugs. Archives of biochemistry and biophysics. 2023 Jul 01;742:109637