Gen RAS trong các khối u não và sự tham gia của microRNA let-7

Samantha Messina1
1Department of Science, Roma Tre University, Viale Guglielmo Marconi 446, 00146, Rome, Italy

Tóm tắt

Tóm tắtGen RAS là các gen điều hòa chính trong nhiều loại ung thư. Nói chung, các khối u do RAS điều khiển có đột biến RAS gây ung thư dẫn đến tiến triển bệnh (ruột kết, phổi, tụy). Ngược lại, các khối u não không nhất thiết phải là ung thư do RAS điều khiển vì đột biến RAS hiếm khi được quan sát thấy. Đặc biệt, glioblastomas (khối u não nguy hiểm nhất) không có vẻ như có các đột biến gen chủ yếu phù hợp cho liệu pháp nhắm mục tiêu. Phương pháp điều trị tiêu chuẩn cho hầu hết các khối u não vẫn tiếp tục tập trung vào phẫu thuật cắt bỏ tối đa, xạ trị và hóa trị. Tuy nhiên, sự hội tụ của các bất thường gen như EGFR, PDGFR và NF1 (một số trong số đó có hiệu quả lâm sàng) với sự kích hoạt của chuỗi RAS/MAPK vẫn được coi là điểm mấu chốt trong sự hình thành glioma, và KRAS chắc chắn là một gen dẫn dắt trong sự hình thành glioma ở chuột. Trong ung thư, microRNA (miRNA) là các RNA nhỏ không mã hóa có vai trò trong việc điều chỉnh quá trình gây ung thư. Tuy nhiên, hậu quả chức năng của sự biểu hiện miRNA bất thường trong ung thư vẫn chưa được hiểu rõ. let-7 mã hóa một miRNA liên gen được phân loại là chất ức chế khối u, ít nhất là trong ung thư phổi. Let-7 ức chế một loạt các gen gây ung thư như RAS, HMGA, c-Myc, cyclin-D và do đó ức chế sự phát triển, phân hóa và tiến triển của ung thư. Các thành viên của gia đình let-7 là những người điều chỉnh trực tiếp các gen thuộc gia đình RAS bằng cách gắn kết với các trình tự trong vùng phi dịch mã 3′ (3′UTR) của chúng. let-7 miRNA tham gia vào hành vi ác tính trong vitro—tăng trưởng, di cư và xâm nhập—của gliomas và các tế bào glioma giống như tế bào gốc cũng như trong các mô hình in vivo của glioblastoma multiforme (GBM) qua ức chế KRAS. Nó cũng làm tăng khả năng kháng với một số tác nhân hóa trị liệu và xạ trị trong GBM. Mặc dù liệu pháp let-7 chưa được thành lập, bài đánh giá này cập nhật trạng thái kiến thức hiện tại về sự đóng góp của miRNA let-7 trong tương tác với KRAS đến quá trình gây ung thư của các khối u não.

Từ khóa

#Ras #ung thư não #microRNA let-7 #glioblastoma #di truyền học ung thư

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