上海交通大学学报(医学版) ›› 2022, Vol. 42 ›› Issue (10): 1474-1481.doi: 10.3969/j.issn.1674-8115.2022.10.014

• 综述 • 上一篇    

肌盲样蛋白1在恶性肿瘤中作用的研究进展

朱楠(), 刘炳亚, 俞焙秦()   

  1. 上海交通大学医学院附属瑞金医院普外科,上海市胃肿瘤重点实验室,上海消化外科研究所,上海 200025
  • 收稿日期:2022-03-28 接受日期:2022-09-15 出版日期:2022-10-28 发布日期:2022-12-02
  • 通讯作者: 俞焙秦 E-mail:znzhunan@sjtu.edu.cn;yubeiqin@126.com
  • 作者简介:朱 楠(1997—),女,硕士生;电子信箱:znzhunan@sjtu.edu.cn
  • 基金资助:
    国家自然科学基金(81902393);上海市自然科学基金(19ZR1431700);上海交通大学医工交叉研究基金(YG2019QNB23)

Advances in the role of muscle blind-like protein 1 in malignant tumors

ZHU Nan(), LIU Bingya, YU Beiqin()   

  1. Shanghai Institute of Digestive Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
  • Received:2022-03-28 Accepted:2022-09-15 Online:2022-10-28 Published:2022-12-02
  • Contact: YU Beiqin E-mail:znzhunan@sjtu.edu.cn;yubeiqin@126.com
  • Supported by:
    National Natural Science Foundation of China(81902393);Natural Science Foundation of Shanghai(19ZR1431700);Interdisciplinary Program of Shanghai Jiao Tong University(YG2019QNB23)

摘要:

肌盲样蛋白1(muscle blind-like protein 1,MBNL1)是一种RNA结合蛋白,其作为前体信使RNA(precursor mRNA,pre-mRNA)的可变剪接因子,在发育过程中起调节作用,有助于对特定转录集的转录后调控。MBNL1可以影响RNA成熟和表达过程的多个步骤,包括pre-mRNA的剪接、降解、RNA输出、稳定性维持、修饰和翻译等。MBNL1最早被认为是强直性肌营养不良发病机制的相关因子,随着研究的深入,其在多种非肿瘤性疾病以及肿瘤性疾病中的作用逐渐凸显。研究表明,MBNL1在多种疾病中表达异常,并且与恶性肿瘤如胃癌、结直肠癌、乳腺癌、前列腺癌、脑胶质瘤、肺癌、血液系统肿瘤等的发生、发展以及转移密切相关。由于细胞种类和发育环境的不同,正常细胞和肿瘤细胞中MBNL1蛋白水平的变化具有多样性。MBNL1既可作为转录激活因子促进肿瘤的发生与发展,也可作为转录阻遏因子抑制肿瘤的生长、转移等过程,在恶性肿瘤的发病过程中发挥重要作用。该文就MBNL1在肿瘤发生发展中的分子机制、生物学特性及其在不同恶性肿瘤中的表达和功能进行综述,为肿瘤的靶向治疗及预后评估提供新的研究思路。

关键词: 肌盲样蛋白1, 可变剪接, 剪接因子, 肿瘤, 分子机制

Abstract:

Muscle blind-like protein 1 (MBNL1) is a class of RNA binding protein. As an alternative splicing factor of precursor mRNA (pre-mRNA), it plays a fundamental role in the regulation of the development process and the post transcriptional regulation of specific transcripts, which affects multiple steps in the process of RNA maturation and expression, including pre-mRNA splicing, degradation, RNA output, stability maintenance, modification and translation. MBNL1 was first considered as a contributing factor in the pathogenesis of myotonic dystrophy. With going deep into the research, its role in a variety of non-tumor and tumor diseases has become increasingly prominent. Studies have shown that MBNL1 is abnormally expressed in many types of tumors and is closely related to the occurrence, development and metastasis of various malignant tumors, such as gastric cancer, colorectal cancer, breast cancer, prostate cancer, glioblastoma, lung cancer, hematological system tumors, etc. According to different cell types and development environments, the changes of MBNL1 protein levels in normal and tumor cells are diverse. MBNL1 can not only act as a transcriptional activator to promote the occurrence and development of tumors, but also play as a transcriptional repressor to inhibit the growth and metastasis of tumors. The present review summarizes the molecular mechanism, biological characteristics, expression and function of MBNL1 in the occurrence and development of various malignancies to provide several new insights into tumor-targeted therapy and prognosis evaluation.

Key words: muscle blind-like protein 1 (MBNL1), alternative splicing, splicing factor, malignant tumor, molecular mechanism

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