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上皮剪接调节蛋白在癌症进展中的潜在机制。

Underlying mechanisms of epithelial splicing regulatory proteins in cancer progression.

机构信息

Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, Qingdao Medical College, Qingdao University, Qingdao, 266021, China.

School of Basic Medical Sciences, Qingdao Medical College, Qingdao University, Qingdao, 266071, China.

出版信息

J Mol Med (Berl). 2022 Nov;100(11):1539-1556. doi: 10.1007/s00109-022-02257-5. Epub 2022 Sep 27.

Abstract

Cancer is the second-leading disease-related cause of global mortality after cardiovascular disease. Despite significant advances in cancer therapeutic strategies, cancer remains one of the major obstacles to human life extension. Cancer pathogenesis is extremely complicated and not fully understood. Epithelial splicing regulatory proteins (ESRPs), including ESRP1 and ESRP2, belong to the heterogeneous nuclear ribonucleoprotein family of RNA-binding proteins and are crucial regulators of the alternative splicing of messenger RNAs (mRNAs). The expression and activity of ESRPs are modulated by various mechanisms, including post-translational modifications and non-coding RNAs. Although a growing body of evidence suggests that ESRP dysregulation is closely associated with cancer progression, the detailed mechanisms remain inconclusive. In this review, we summarize recent findings on the structures, functions, and regulatory mechanisms of ESRPs and focus on their underlying mechanisms in cancer progression. We also highlight the clinical implications of ESRPs as prognostic biomarkers and therapeutic targets in cancer treatment. The information reviewed herein could be extremely beneficial to the development of individualized therapeutic strategies for cancer patients.

摘要

癌症是继心血管疾病之后全球第二大与疾病相关的死亡原因。尽管癌症治疗策略取得了重大进展,但癌症仍然是人类延长寿命的主要障碍之一。癌症的发病机制非常复杂,尚未完全了解。上皮剪接调节蛋白(ESRPs),包括 ESRP1 和 ESRP2,属于 RNA 结合蛋白的异质核核糖核蛋白家族,是信使 RNA(mRNA)选择性剪接的关键调节因子。ESRP 的表达和活性受到多种机制的调节,包括翻译后修饰和非编码 RNA。尽管越来越多的证据表明 ESRP 失调与癌症进展密切相关,但详细的机制仍不清楚。在这篇综述中,我们总结了 ESRPs 的结构、功能和调节机制的最新发现,并重点介绍了它们在癌症进展中的潜在机制。我们还强调了 ESRPs 作为癌症治疗中预后生物标志物和治疗靶点的临床意义。本文综述的信息对于为癌症患者制定个体化治疗策略非常有帮助。

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