PIK3R2 predicts poor outcomes for patients with melanoma and contributes to the malignant progression via PI3K/AKT/NF-κB axis

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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.
Funding Information
  • Science Plan Project of Suzhou (No. SYSD2019118, SYS2020151, SYS2020161)

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