[Research Advances of m⁶A RNA Methylation in Non-small Cell Lung Cancer]

Zhongguo Fei Ai Za Zhi. 2020 Nov 20;23(11):961-969. doi: 10.3779/j.issn.1009-3419.2020.102.35.
[Article in Chinese]

Abstract

N6-methyladenosine is one of the most prevalent mRNA modification in eukaryotes. The regulation of this pervasive mark is a dynamic and reversible process. m⁶A RNA methylation is catalyzed by m⁶A writers, removed by m⁶A erasers and recognized by m⁶A readers, thereby regulating multiple RNA processes including alternative splicing, nuclear export, degradation and translation. Accumulated evidence suggests that m⁶A modification plays a crucial role in the pathogenic mechanism and malignant progression in non-small cell lung cancer (NSCLC), including cell survival, proliferation, migration, invasion, tumor metastasis and drug resistance. Moreover, the expression of m⁶A and its related proteins are dysregulated in clinical samples and circulating tumor cells (CTCs) of lung cancer patients, indicating that m⁶A modification may serve as a novel potential biomarker for the diagnosis and prognosis of lung cancer. In this review, by summarizing a great number of recent reports related to m⁶A's function and its modulators, we aim to provide a new insight on the early diagnosis and drug development in NSCLC therapy. .

【中文题目:m⁶A RNA甲基化在非小细胞肺癌中的 研究进展】 【中文摘要:m⁶A修饰是真核生物mRNA中最丰富的修饰之一,该过程受m⁶A甲基转移酶和去甲基化酶的共同调控。m⁶A修饰后的RNA能够被m⁶A识别蛋白特异性识别并结合,进而介导RNA的剪接、成熟、出核、降解和翻译等。目前国内外对于m⁶A修饰及其相关蛋白如何参与非小细胞肺癌发生发展的研究,主要集中于细胞恶性增殖、迁移、侵袭、转移和耐药等方面。m⁶A修饰相关蛋白在肺癌组织标本和血液循环肿瘤细胞(circulating tumor cell, CTC)中表达异常,有望成为肺癌诊断和预后判断的潜在分子标志物。本文围绕m⁶A修饰相关蛋白的组成、作用方式、在非小细胞肺癌恶性进展中的生物学功能,以及针对m⁶A修饰的靶向治疗等方面的研究进展进行综述,旨在为非小细胞肺癌的早期临床诊断和靶向药物的开发提供新思路。 】 【中文关键词:肺肿瘤;m⁶A修饰;RNA甲基化;表观遗传修饰】.

Keywords: Epigenetic modification; Lung neoplasms; N6-methyladenosine; RNA methylation.

Publication types

  • Review

MeSH terms

  • Adenosine / metabolism
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Methylation
  • Molecular Targeted Therapy
  • RNA, Messenger / metabolism*

Substances

  • RNA, Messenger
  • Adenosine

Grants and funding

本文受国家自然科学基金项目(No.81302002)、天津市自然科学基金项目(No.17JCQNJC11700、No.18JCYBJC92100和No.14JCQNJC12300)和天津医科大学总医院孵育基金项目(No.ZYYFY2016013)资助