Nội dung được dịch bởi AI, chỉ mang tính chất tham khảo
Nhắm mục tiêu vào SMYD2 ức chế sự hình thành mạch và tăng cường hiệu quả của apatinib bằng cách ức chế EGFL7 trong ung thư đại trực tràng
Tóm tắt
Sự hình thành mạch là một yếu tố thiết yếu ảnh hưởng đến sự xuất hiện và phát triển của các khối u rắn. Chất chứa miền SET và MYND 2 (SMYD2) hoạt động như một oncoprotein trong nhiều loại ung thư. Tuy nhiên, liệu SMYD2 có tham gia vào sự hình thành mạch trong khối u hay không vẫn còn chưa rõ ràng. Tại đây, chúng tôi báo cáo rằng sự biểu hiện của SMYD2 có liên quan đến mật độ vi mạch trong mô ung thư đại trực tràng (CRC). SMYD2 thúc đẩy sự hình thành mạch của CRC trong ống nghiệm và trong mô hình sống. Về mặt cơ chế, SMYD2 tương tác vật lý với HNRNPK và trung gian cho sự methyl hóa lysine tại K422 của HNRNPK, điều này làm tăng đáng kể hoạt động gắn RNA. HNRNPK hoạt động bằng cách gắn và ổn định mRNA của EGFL7. Như một chất kích thích hình thành mạch, EGFL7 tăng cường sự hình thành mạch của CRC. H3K4me3 duy trì bởi PHF8 trung gian cho sự biểu hiện quá mức bất thường của SMYD2 trong CRC. Hơn nữa, nhắm mục tiêu vào SMYD2 làm chặn sự hình thành mạch ở mô ghép của khối u. Việc điều trị bằng BAY-598, một chất ức chế chức năng của SMYD2, cũng có thể hợp tác với apatinib trong mô ghép lấy từ bệnh nhân. Tổng thể, các phát hiện của chúng tôi tiết lộ một trục điều tiết mới của sự hình thành mạch trong CRC và cung cấp một chiến lược tiềm năng cho liệu pháp chống hình thành mạch.
Từ khóa
#SMYD2 #sự hình thành mạch #ung thư đại trực tràng #EGFL7 #HNRNPK #điều trị chống hình thành mạchTài liệu tham khảo
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