Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, 727 Jingming South Road, Kunming, 650500, China.
Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, 650500, China.
Cell Commun Signal. 2020 Nov 4;18(1):175. doi: 10.1186/s12964-020-00607-9.
The regulation of the translation of messenger RNA (mRNA) in eukaryotic cells is critical for gene expression, and occurs principally at the initiation phase which is mainly regulated by eukaryotic initiation factors (eIFs). eIFs are fundamental for the translation of mRNA and as such act as the primary targets of several signaling pathways to regulate gene expression. Mis-regulated mRNA expression is a common feature of tumorigenesis and the abnormal activity of eIF complexes triggered by upstream signaling pathways is detected in many tumors, leading to the selective translation of mRNA encoding proteins involved in tumorigenesis, metastasis, or resistance to anti-cancer drugs, and making eIFs a promising therapeutic target for various types of cancers. Here, we briefly outline our current understanding of the biology of eIFs, mainly focusing on the effects of several signaling pathways upon their functions and discuss their contributions to the initiation and progression of tumor growth. An overview of the progress in developing agents targeting the components of translation machinery for cancer treatment is also provided. Video abstract.
真核细胞中信使 RNA(mRNA)翻译的调控对基因表达至关重要,主要发生在起始阶段,主要受真核起始因子(eIFs)调控。eIFs 是 mRNA 翻译的基础,因此是几种信号通路调节基因表达的主要靶点。mRNA 表达失调是肿瘤发生的常见特征,上游信号通路触发的 eIF 复合物异常活性在许多肿瘤中被检测到,导致与肿瘤发生、转移或对抗癌药物耐药相关的编码蛋白质的 mRNA 选择性翻译,使 eIF 成为各种类型癌症有前途的治疗靶点。在这里,我们简要概述了我们对 eIF 生物学的现有理解,主要集中在几种信号通路对其功能的影响,并讨论了它们对肿瘤生长起始和进展的贡献。还提供了靶向翻译机制成分治疗癌症的进展概述。视频摘要。