Smialek Maciej J, Ilaslan Erkut, Sajek Marcin P, Jaruzelska Jadwiga
Institute of Human Genetics, Polish Academy of Sciences, Strzeszynska 32, 60-479 Poznan, Poland.
Cancers (Basel). 2021 Jan 3;13(1):129. doi: 10.3390/cancers13010129.
Until recently, post-transcriptional gene regulation (PTGR), in contrast to transcriptional regulation, was not extensively explored in cancer, even though it seems to be highly important. PUM proteins are well described in the PTGR of several organisms and contain the PUF RNA-binding domain that recognizes the UGUANAUA motif, located mostly in the 3' untranslated region (3'UTR) of target mRNAs. Depending on the protein cofactors recruited by PUM proteins, target mRNAs are directed towards translation, repression, activation, degradation, or specific localization. Abnormal profiles of PUM expression have been shown in several types of cancer, in some of them being different for PUM1 and PUM2. This review summarizes the dysregulation of PUM1 and PUM2 expression in several cancer tissues. It also describes the regulatory mechanisms behind the activity of PUMs, including cooperation with microRNA and non-coding RNA machineries, as well as the alternative polyadenylation pathway. It also emphasizes the importance of future studies to gain a more complete picture of the role of PUM proteins in different types of cancer. Such studies may result in identification of novel targets for future cancer therapies.
直到最近,与转录调控相比,转录后基因调控(PTGR)在癌症研究中并未得到广泛探索,尽管它似乎极为重要。PUM蛋白在几种生物体的PTGR中已有充分描述,并且含有识别UGUANAUA基序的PUF RNA结合结构域,该基序大多位于靶mRNA的3'非翻译区(3'UTR)。根据PUM蛋白招募的蛋白质辅因子不同,靶mRNA会被导向翻译、抑制、激活、降解或特定定位。在几种癌症类型中已显示出PUM表达的异常模式,其中一些癌症中PUM1和PUM2的表达模式有所不同。本综述总结了几种癌组织中PUM1和PUM2表达的失调情况。它还描述了PUM活性背后的调控机制,包括与微小RNA和非编码RNA机制的合作,以及可变聚腺苷酸化途径。它还强调了未来研究的重要性,以便更全面地了解PUM蛋白在不同类型癌症中的作用。此类研究可能会促成未来癌症治疗新靶点的发现。