Department of Basic Sciences, The Commonwealth Medical College, 525 Pine Street, Scranton, PA 18509, USA.
J Cancer. 2013;4(2):96-103. doi: 10.7150/jca.5470. Epub 2013 Jan 5.
RNA processing involves a variety of processes affecting gene expression, including the removal of introns through RNA splicing, as well as 3' end processing (cleavage and polyadenylation). Alternative RNA processing is fundamentally important for gene regulation, and aberrant processing is associated with the initiation and progression of cancer. Deregulated Wnt signaling, which is the initiating event in the development of most cases of human colorectal cancer (CRC), has been linked to modified RNA processing, which may contribute to Wnt-mediated colonic carcinogenesis. Crosstalk between Wnt signaling and alternative RNA splicing with relevance to CRC includes effects on the expression of Rac1b, an alternatively spliced gene associated with tumorigenesis, which exhibits alternative RNA splicing that is influenced by Wnt activity. In addition, Tcf4, a crucial component of Wnt signaling, also exhibits alternative splicing, which is likely involved in colonic tumorigenesis. Modulation of 3' end formation, including of the Wnt target gene COX-2, also can influence the neoplastic process, with implications for CRC. While many human genes are dependent on introns and splicing for normal levels of gene expression, naturally intronless genes exist with a unique metabolism that allows for intron-independent gene expression. Effects of Wnt activity on the RNA metabolism of the intronless Wnt-target gene c-jun is a likely contributor to cancer development. Further, butyrate, a breakdown product of dietary fiber and a histone deacetylase inhibitor, upregulates Wnt activity in CRC cells, and also modulates RNA processing; therefore, the interplay between Wnt activity, the modulation of this activity by butyrate, and differential RNA metabolism in colonic cells can significantly influence tumorigenesis. Determining the role played by altered RNA processing in Wnt-mediated neoplasia may lead to novel interventions aimed at restoring normal RNA metabolism for therapeutic benefit. Therefore, this minireview presents a brief overview of several aspects of RNA processing of relevance to cancer, which potentially influence, or are influenced by, Wnt signaling activity.
RNA 加工涉及多种影响基因表达的过程，包括通过 RNA 剪接去除内含子，以及 3'端加工（切割和多聚腺苷酸化）。可变 RNA 加工对于基因调控至关重要，异常加工与癌症的发生和发展有关。Wnt 信号的失调是大多数人类结直肠癌（CRC）发展的起始事件，与修饰的 RNA 加工有关，这可能有助于 Wnt 介导的结直肠癌变。与 CRC 相关的 Wnt 信号和可变 RNA 剪接的串扰包括对 Rac1b 表达的影响，Rac1b 是一个与肿瘤发生相关的可变剪接基因，其可变剪接受 Wnt 活性的影响。此外，Wnt 信号的关键组成部分 Tcf4 也表现出可变剪接，这可能与结直肠肿瘤发生有关。3'端形成的调节，包括 Wnt 靶基因 COX-2 的调节，也可以影响肿瘤发生过程，对 CRC 有影响。虽然许多人类基因依赖于内含子和剪接来维持正常的基因表达水平，但也存在天然无内含子的基因，它们具有独特的代谢方式，可以实现无内含子的基因表达。Wnt 活性对无内含子 Wnt 靶基因 c-jun 的 RNA 代谢的影响可能是癌症发展的一个原因。此外，膳食纤维的分解产物和组蛋白去乙酰化酶抑制剂丁酸盐可上调 CRC 细胞中的 Wnt 活性，并调节 RNA 加工；因此，Wnt 活性、丁酸盐对这种活性的调节以及结肠细胞中不同的 RNA 代谢之间的相互作用会显著影响肿瘤发生。确定改变的 RNA 加工在 Wnt 介导的肿瘤形成中所起的作用可能会导致新的干预措施的出现，这些干预措施旨在恢复正常的 RNA 代谢以获得治疗益处。因此，这篇综述简要介绍了与癌症相关的几个 RNA 加工方面，这些方面可能影响或受 Wnt 信号活性的影响。
