Abstract
Background
Melanoma is an aggressive form of skin cancer worldwide. Phosphoinositide-3-kinase regulatory subunit 2 (PIK3R2) exerts carcinogenic roles in various tumors. So far, the function and mechanism of PIK3R2 in melanoma are not been fully clarified.
Objective
We aimed to clarify the role of PIK3R2 in melanoma.
Methods
PIK3R2 expressions in melanoma clinical tissues and melanoma cells were measured using quantitative real-time PCR and Western blot. In addition, PIK3R2 expressions in different tumor stages of melanoma were determined by immunohistochemistry assay. Meanwhile, PIK3R2 function was evaluated using loss or gain-of-function assays, Cell Counting Kit-8 assay, flow cytometry, and Transwell analysis. Furthermore, PIK3R2 mechanism in melanoma was assessed by a series of rescue experiments.
Results
PIK3R2 was highly expressed in melanoma tissues and cells, and PIK3R2 expressions were the highest in Stage IV. Functionally, PIK3R2 knockdown repressed melanoma cell proliferation, invasion, epithelial-mesenchymal transition, and facilitated cell apoptosis. Also, PIK3R2 overexpression produced an opposite trend. Mechanistically, PIK3R2 facilitated melanoma progression by activating PI3K/AKT/NF-κB pathway. Furthermore, PIK3R2 knockdown restrained the melanoma tumor growth in vivo.
Conclusions
PIK3R2 aggravated melanoma by activating PI3K/AKT/NF-κB pathway, prompting that PIK3R2 might be a therapeutic target for melanoma.
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Data availability
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
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Acknowledgements
This work was generously supported by the Natural Science Foundation of Jiangsu Province of China (Grant No.BK20191176 ), the Jiangsu Province Maternal and Child Health Research Project (Grant No. F202116), Gusu Health Talent Project of Suzhou City (Grant No.GSWS2020049), National Tutorial System Training Program for key Young Health Talents in Suzhou (Grant No. Qngg2021011), the Scientific Research Project of Jiangsu Health Commission (Grant No. M2022062), Suzhou Science and Technology Development Plan [People's Livelihood Science and Technology (Grant No. SYSD2019118, SYS2020151 and SYS2020161)], Suzhou Science and Technology Development Plan [Innovation in medical and health technology (Grant No. SKY2022055, SKY2022173, SKY2022174 and SKJYD2021093)] and Key Laboratory of Structural Deformities in Children of Suzhou (Grant No. SZS2022018. The funders had no role in the study design, data collection and analysis, decision to publish, or in the preparation of the manuscript.
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All animal research was conducted with the approval of the Ethics Committee of Nanjing Pukou Central Hospital (Pukou Branch Hospital of Jiangsu Province Hospital).
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Wang, J., Cai, S., Xiong, Q. et al. PIK3R2 predicts poor outcomes for patients with melanoma and contributes to the malignant progression via PI3K/AKT/NF-κB axis. Clin Transl Oncol 25, 1402–1412 (2023). https://doi.org/10.1007/s12094-022-03036-x
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DOI: https://doi.org/10.1007/s12094-022-03036-x