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

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.