Comprehensive analyses of molecular features, prognostic values, and regulatory functionalities of m6A-modified long non-coding RNAs in lung adenocarcinoma.

IF 5.7 2区 医学 Q1 Medicine
Yili Ping, Jingjuan Huang, Jichao Zhu, Zujun Sun, Anquan Shang, Chen Chen, Wenfang Liu, Dong Li
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引用次数: 0

Abstract

Background: Lung adenocarcinoma (LUAD) has a high incidence and recurrence rate. N6-methyladenosine (m6A) modification of RNA has become a promising epigenetic marker in tumors. The dysregulation of both RNA m6A levels and m6A regulator expression levels reportedly affects essential biological processes in various tumors. Long non-coding RNAs (lncRNAs), a subgroup of RNAs over 200 nucleotides in length that do not code for protein, can be modified and regulated by m6A, but the relevant profile in LUAD remains unclear.

Results: The m6A levels of total RNA were decreased in LUAD tumor tissues and cells. Multiple m6A regulators were abnormally expressed at both the RNA and protein levels, and were related in expression patterns and functionally synergistic. Our microarray revealed 2846 m6A-modified lncRNA transcripts as well as its molecular features, 143 of which were differentially m6A-modified and manifested a negative correlation between expression levels and m6A modification levels. More than half of the differentially m6A-modified lncRNAs associated with dysregulated expression. The 6-MRlncRNA risk signature was a reliable indicator for assessing survival time of LUAD patients. The competitive endogenous regulatory network suggested a potential m6A-induced pathogenicity in LUAD.

Conclusions: These data have demonstrated that differential RNA m6A modification and m6A regulator expression levels were identified in LUAD patients. In addition, this study provides evidence increasing the understanding of molecular features, prognostic values, and regulatory functionalities of m6A-modified lncRNAs in LUAD.

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m6a修饰的长链非编码rna在肺腺癌中的分子特征、预后价值和调控功能的综合分析
背景:肺腺癌(LUAD)具有较高的发病率和复发率。n6 -甲基腺苷(m6A)修饰RNA已成为一种很有前景的肿瘤表观遗传标记。据报道,RNA m6A水平和m6A调节因子表达水平的失调影响各种肿瘤的基本生物学过程。长链非编码rna (Long non-coding rna, lncRNAs)是一种长度超过200个核苷酸且不编码蛋白质的rna亚群,可以被m6A修饰和调节,但在LUAD中的相关谱尚不清楚。结果:LUAD肿瘤组织和细胞中总RNA m6A水平降低。多个m6A调节因子在RNA和蛋白水平上均异常表达,且在表达模式上相关,在功能上协同。我们的基因芯片显示了2846个m6A修饰的lncRNA转录本及其分子特征,其中143个是m6A差异修饰,表达水平与m6A修饰水平呈负相关。超过一半的m6a修饰的差异lncrna与表达失调有关。6-MRlncRNA风险标志是评估LUAD患者生存时间的可靠指标。竞争性内源性调控网络表明m6a可能诱导LUAD的致病性。结论:这些数据表明,在LUAD患者中发现了不同的RNA m6A修饰和m6A调节因子表达水平。此外,本研究提供的证据增加了对m6a修饰的lncrna在LUAD中的分子特征、预后价值和调节功能的理解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Clinical Epigenetics
Clinical Epigenetics Biochemistry, Genetics and Molecular Biology-Developmental Biology
CiteScore
8.90
自引率
5.30%
发文量
150
审稿时长
12 weeks
期刊介绍: Clinical Epigenetics, the official journal of the Clinical Epigenetics Society, is an open access, peer-reviewed journal that encompasses all aspects of epigenetic principles and mechanisms in relation to human disease, diagnosis and therapy. Clinical trials and research in disease model organisms are particularly welcome.
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