Wang Hao, Ding Nannan, Guo Jian, Xia Jiazeng, Ruan Yulan
Department of General Surgery and Translational Medicine Center, Nanjing Medical University Affiliated Wuxi Second Hospital, Wuxi, Jiangsu, 214002, China.
Department of ophthalmology and Translational Medicine Center, Nanjing Medical University Affiliated Wuxi Second Hospital, Wuxi, Jiangsu, 214002, China.
Tumour Biol. 2016 Nov;37(11):14451-14461. doi: 10.1007/s13277-016-5397-z. Epub 2016 Sep 19.
Defects in the adenosine-uridine (AU)-rich elements (AREs), which mediate post-transcriptional regulation, play important roles in cancers. Both tristetraprolin (TTP, also known as TIS11 and ZFP36) and human antigen R (HuR, also known as ELAVL1) are two important and closely related AU-rich RNA-binding proteins (ARE-BPs). High-expression or aberrant nuclear/cytoplasmic distribution of HuR and decreased TTP have been found in many types of cancers. TTP mediates the decay of target mRNAs, whereas HuR generally stabilizes target transcripts and promotes translation of certain mRNAs. Furthermore, thousands of overlapping binding sites of TTP and HuR were found in more than 1300 genes. RNA-IP experiments also indicated that TTP can bind directly to and destabilize HuR mRNA. The dysregulation of TTP and HuR has been found to play an important role in the progression of cancers, including inflammation-related cancer, as well as in proliferation, apoptosis, angiogenesis, metastasis, invasion, and chemotherapy resistance. In this review, we provided an overview of the role of TTP and HuR, as well as the underlying mechanisms of the TTP-HuR axis in cancers.
富含腺苷-尿苷（AU）元件（AREs）的缺陷介导转录后调控，在癌症中发挥重要作用。锌指蛋白36（TTP，也称为TIS11和ZFP36）和人抗原R（HuR，也称为ELAVL1）都是两种重要且密切相关的富含AU的RNA结合蛋白（ARE-BPs）。在许多类型的癌症中都发现了HuR的高表达或异常核/质分布以及TTP的减少。TTP介导靶mRNA的降解，而HuR通常稳定靶转录本并促进某些mRNA的翻译。此外，在1300多个基因中发现了数千个TTP和HuR的重叠结合位点。RNA免疫沉淀实验还表明，TTP可以直接结合并使HuR mRNA不稳定。已发现TTP和HuR的失调在癌症进展中起重要作用，包括炎症相关癌症，以及在增殖、凋亡、血管生成、转移、侵袭和化疗耐药性方面。在本综述中，我们概述了TTP和HuR的作用，以及TTP-HuR轴在癌症中的潜在机制。
