Làm giảm KPNA2 thúc đẩy ferroptosis trong ung thư thanh quản bằng cách kích hoạt con đường tín hiệu FoxO

Mimi Xu1, Xiaoqi Hu1, Zhixue Xiao1, Siyi Zhang1, Zhongming Lu1
1Department of Otorhinolaryngology Head and Neck Surgery, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou City, China

Tóm tắt

Chúng tôi nhằm mục đích làm rõ vai trò cụ thể của Karyopherin α2 (KPNA2) trong quá trình tiến triển của ung thư thanh quản, một loại khối u ác tính với hiệu quả điều trị kém. Chúng tôi đã thực hiện phân tích tin sinh học để thu được các gen biểu hiện khác nhau liên quan đến ferroptosis. KPNA2 đã được chọn lọc. Sau đó, phép thử CCK-8, phép thử lành vết thương và phép thử transwell đã được sử dụng để làm rõ sự thay đổi trong khả năng sinh sản, di chuyển và xâm lấn của tế bào ung thư thanh quản sau khi làm tắt KPNA2. Nồng độ ion sắt, glutathione, superoxide dismutase và malondialdehyde đã được đánh giá bằng các bộ phát hiện tương ứng. Mức độ biểu hiện của cyclooxygenase 2, thành viên 4 của họ enzyme Acyl-CoA synthetase dài chuỗi, glutathione peroxidase 4, forkhead box O (FoxO)1a và FoxO3a đã được xác định bằng phương pháp Western Blot. Tổng cộng đã thu được 45 gen biểu hiện khác nhau liên quan đến ferroptosis trong ung thư thanh quản, và KPNA2 đã được chọn sau phân tích tin sinh học. Trong các tế bào ung thư thanh quản do ferroptosis gây ra, khả năng sống sót của tế bào, tỷ lệ di chuyển, khả năng xâm lấn, và biểu hiện của glutathione peroxidase 4, glutathione và superoxide dismutase tiếp tục giảm, trong khi biểu hiện của cyclooxygenase 2, thành viên 4 của họ enzyme Acyl-CoA synthetase dài chuỗi, ion sắt, và malondialdehyde tiếp tục tăng sau khi làm tắt KPNA2. Mức độ biểu hiện của FoxO1a và FoxO3a trong các tế bào ung thư thanh quản đã tăng lên khi làm tắt KPNA2. KPNA2 có thể là một mục tiêu điều trị đầy hứa hẹn cho ung thư thanh quản. Việc hạ thấp KPNA2 có thể thúc đẩy ferroptosis trong ung thư thanh quản bằng cách kích thích con đường tín hiệu FoxO.

Từ khóa

#Karyopherin α2 #KPNA2 #ferroptosis #ung thư thanh quản #con đường tín hiệu FoxO

Tài liệu tham khảo

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