YTHDF1 thúc đẩy sự tiến triển của ung thư biểu mô gan thông qua việc kích hoạt con đường tín hiệu PI3K/AKT/mTOR và gây ra quá trình chuyển đổi biểu mô - trung mô
Tóm tắt
Chỉnh sửa N6-methyladenosine (m6A), là dạng chỉnh sửa RNA phong phú nhất, tham gia rộng rãi vào các quá trình sinh lý và liên quan đến sự tiến triển của nhiều loại bệnh, đặc biệt là ung thư. Protein gắn RNA YTH N6-methyladenosine 1 (YTHDF1) là một protein “đọc” m6A quan trọng, đã được báo cáo trong nhiều loại ung thư. Tuy nhiên, vai trò và cơ chế phân tử của YTHDF1 trong ung thư biểu mô gan (HCC) vẫn chưa được làm sáng tỏ hoàn toàn.
Dựa trên các cơ sở dữ liệu bioinformatics khác nhau, q-RT PCR, blot miền và một hồ sơ vi mô mô chứa 90 mẫu HCC, chúng tôi đã kiểm tra sự biểu hiện của YTHDF1 trong HCC. Sau đó, chúng tôi đã áp dụng các thí nghiệm mất chức năng để khám phá vai trò của YTHDF1 trong HCC thông qua các thí nghiệm trong ống nghiệm và trong cơ thể. Cuối cùng, chúng tôi tiến hành phân tích làm giàu tập hợp gen (GSEA) để dự đoán con đường tín hiệu tiềm ẩn của YTHDF1 liên quan đến HCC và xác minh dự đoán này.
YTHDF1 đã được biểu hiện cao trong HCC và có mối liên hệ với độ ác tính của HCC. Việc loại bỏ YTHDF1 đã làm suy yếu rõ rệt quá trình sinh sản, di cư, xâm lấn và chu kỳ tế bào của các tế bào HCC. Về mặt cơ chế, YTHDF1 thúc đẩy sự phát triển của các tế bào HCC thông qua việc kích hoạt con đường tín hiệu PI3K/AKT/mTOR. Hơn nữa, chúng tôi cũng đã chứng minh rằng quá trình chuyển đổi biểu mô - trung mô (EMT) đã làm trung gian hiệu ứng thúc đẩy của YTHDF1 đối với sự di cư và xâm lấn của các tế bào HCC.
YTHDF1 góp phần vào sự tiến triển của HCC bằng cách kích hoạt con đường tín hiệu PI3K/AKT/mTOR và gây ra EMT.
Từ khóa
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