Maltseva Diana, Tonevitsky Alexander
Faculty of Biology and Biotechnology, HSE University, Moscow, Russia.
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.
Front Mol Biosci. 2023 Dec 1;10:1326148. doi: 10.3389/fmolb.2023.1326148. eCollection 2023.
Alternative splicing is often deregulated in cancer, and cancer-specific isoform switches are part of the oncogenic transformation of cells. Accumulating evidence indicates that isoforms of the multifunctional cell-surface glycoprotein CD44 play different roles in cancer cells as compared to normal cells. In particular, the shift of CD44 isoforms is required for epithelial to mesenchymal transition (EMT) and is crucial for the maintenance of pluripotency in normal human cells and the acquisition of cancer stem cells phenotype for malignant cells. The growing and seemingly promising use of splicing inhibitors for treating cancer and other pathologies gives hope for the prospect of using such an approach to regulate CD44 alternative splicing. This review integrates current knowledge about regulating CD44 alternative splicing by RNA-binding proteins.
可变剪接在癌症中常常失调，癌症特异性的异构体转换是细胞致癌转化的一部分。越来越多的证据表明，多功能细胞表面糖蛋白CD44的异构体在癌细胞中与正常细胞相比发挥着不同的作用。特别是，CD44异构体的转变是上皮-间质转化（EMT）所必需的，对于维持正常人细胞的多能性以及恶性细胞获得癌症干细胞表型至关重要。用于治疗癌症和其他疾病的剪接抑制剂的使用日益增加且前景似乎光明，这为使用这种方法调节CD44可变剪接带来了希望。本综述整合了目前关于RNA结合蛋白调节CD44可变剪接的知识。
