可变剪接与胃癌。

Alternative RNA splicing and gastric cancer.

机构信息

Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang 110001, China.

Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, Key Laboratory of Cancer Etiology and Prevention (China Medical University), Liaoning Provincial Education Department, Shenyang 110001, China.

出版信息

Mutat Res Rev Mutat Res. 2017 Jul;773:263-273. doi: 10.1016/j.mrrev.2016.07.011. Epub 2016 Jul 29.

Abstract

Alternative splicing (AS) linked to diseases, especially to tumors. Recently, more and more studies focused on the relationship between AS and gastric cancer (GC). This review surveyed the hot topic from four aspects: First, the common types of AS in cancer, including exon skipping, intron retention, mutually exclusive exon, alternative 5 ' or 3' splice site, alternative first or last exon and alternative 3' untranslated regions. Second, basic mechanisms of AS and its relationship with cancer. RNA splicing in eukaryotes follows the GT-AG rule by both cis-elements and trans-acting factors regulatory. Through RNA splicing, different proteins with different forms and functions can be produced and may be associated with carcinogenesis. Third, AS types of GC-related genes and their splicing variants. In this paper, we listed 10 common genes with AS and illustrated its possible molecular mechanisms owing to genetic variation (mutation and /or polymorphism). Fourth, the splicing variants of GC-associated genes and gastric carcinogenesis, invasion and metastasis. Many studies have found that the different splicing variants of the same gene are differentially expressed in GC and its precancerous diseases, suggesting AS has important implications in GC development. Taking together, this review highlighted the role of AS and splicing variants in the process of GC. We hope that this is not only beneficial to advances in the study field of GC, but also can provide valuable information to other similar tumor research.Although we already know some gene splicing and splicing variants play an important role in the development of GC, but many phenomena and mechanisms are still unknown. For example, how the tumor microenvironment and signal transduction pathway effect the forming and function of AS? Unfortunately, this review did not cover the contents because the current study is limited. It is no doubt that clarifying the phenomena and mechanisms of these unknown may help to reveal the relationship of AS with complex tumor genetic variation and the occurrence and development of tumors.

摘要

可变剪接(AS)与疾病相关,尤其是肿瘤。最近,越来越多的研究集中在 AS 与胃癌(GC)之间的关系上。本综述从四个方面调查了这一热门话题:首先,癌症中常见的 AS 类型,包括外显子跳跃、内含子保留、互斥外显子、选择性 5'或 3'剪接位点、选择性第一或最后外显子和选择性 3'非翻译区。其次,AS 的基本机制及其与癌症的关系。真核生物的 RNA 剪接遵循 cis 元件和反式作用因子调节的 GT-AG 规则。通过 RNA 剪接,可以产生不同形式和功能的不同蛋白质,可能与致癌作用有关。第三,GC 相关基因的 AS 类型及其剪接变体。在本文中,我们列出了 10 个常见的具有 AS 的基因,并说明了由于遗传变异(突变和/或多态性)导致的其可能的分子机制。第四,GC 相关基因的剪接变体与胃癌的发生、侵袭和转移。许多研究发现,同一基因的不同剪接变体在 GC 及其癌前病变中的表达不同,提示 AS 在 GC 发生发展中具有重要意义。综上所述,本综述强调了 AS 和剪接变体在 GC 发生发展过程中的作用。我们希望这不仅有助于 GC 研究领域的进展,也能为其他类似肿瘤的研究提供有价值的信息。虽然我们已经知道一些基因剪接和剪接变体在 GC 的发展中起着重要作用,但仍有许多现象和机制尚不清楚。例如,肿瘤微环境和信号转导途径如何影响 AS 的形成和功能?不幸的是,本综述没有涵盖这些内容,因为目前的研究有限。毫无疑问,阐明这些未知现象和机制可能有助于揭示 AS 与复杂肿瘤遗传变异以及肿瘤发生和发展的关系。

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