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构建 lncRNA-m6A 基因-mRNA 调控网络,鉴定与肺腺癌进展相关的 m6A 相关 lncRNAs。

Construction of lncRNA-m6A gene-mRNA regulatory network to identify m6A-related lncRNAs associated with the progression of lung adenocarcinoma.

机构信息

Department of Oncology Radiotherapy, First Affiliated Hospital of Xi'an Jiaotong University, No. 277, Yanta West Road, Yanta District, Xi'an, Shaanxi Province, 710061, China.

Department of Oncology, The Eighth Hospital of Wuhan, No. 1241 Zhongshan Avenue, Jiang'an District, Wuhan, Hubei Province, 430010, China.

出版信息

BMC Pulm Med. 2023 Aug 3;23(1):284. doi: 10.1186/s12890-023-02545-x.

Abstract

BACKGROUND

We evaluated the prognostic value of m6A-related long noncoding RNAs (lncRNAs) in lung adenocarcinoma (LUAD).

METHODS

The expression levels of lncRNAs and mRNAs in LUAD and normal adjacent tissues from The Cancer Genome Atlas dataset were analyzed using the limma package. m6A enzyme-related differentially expressed lncRNAs and mRNAs were identified and used to construct a regulatory network. Survival analysis was performed and the correlation between lncRNAs, m6A regulators, and mRNAs was analyzed; followed by functional enrichment analysis.

RESULTS

A comparison of LUAD samples and normal tissues identified numerous differentially expressed lncRNAs and mRNAs, demonstrating that a comprehensive network was established. Two lncRNAs and six mRNAs were selected as prognosis related factors including SH3PXD2A-AS1, MAD2L1, CCNA2, and CDC25C. The pathological stage and recurrence status were identified as independent clinical factors (P < 0.05). The expression levels of these RNAs in the different clinical groups were consistent with those in the different risk groups. The interactions of m6A proteins, two lncRNAs, and six mRNAs were predicted, and functional analysis showed that m6A target mRNAs were involved in the cell cycle, progesterone-mediated oocyte maturation, and oocyte meiosis pathways.

CONCLUSIONS

These m6A target lncRNAs and mRNAs may be promising biomarkers for predicting clinical prognosis, and the lncRNA-m6A regulator-mRNA regulatory network could improve our understanding of m6A modification in LUAD progression.

摘要

背景

我们评估了 m6A 相关长链非编码 RNA(lncRNA)在肺腺癌(LUAD)中的预后价值。

方法

使用 limma 软件包分析了来自癌症基因组图谱数据集的 LUAD 和正常相邻组织中的 lncRNA 和 mRNA 的表达水平。鉴定出 m6A 酶相关差异表达的 lncRNA 和 mRNA,并用于构建调控网络。进行生存分析,分析 lncRNA、m6A 调节因子和 mRNAs 之间的相关性;然后进行功能富集分析。

结果

比较 LUAD 样本和正常组织,发现了大量差异表达的 lncRNA 和 mRNA,表明建立了一个全面的网络。选择了两个 lncRNA 和六个 mRNAs 作为与预后相关的因素,包括 SH3PXD2A-AS1、MAD2L1、CCNA2 和 CDC25C。病理分期和复发状态被确定为独立的临床因素(P<0.05)。这些 RNA 在不同临床组中的表达水平与不同风险组中的表达水平一致。预测了 m6A 蛋白、两个 lncRNA 和六个 mRNAs 的相互作用,功能分析表明 m6A 靶 mRNAs 参与了细胞周期、孕激素介导的卵母细胞成熟和卵母细胞减数分裂途径。

结论

这些 m6A 靶 lncRNA 和 mRNAs 可能是预测临床预后的有前途的生物标志物,lncRNA-m6A 调节因子-mRNA 调控网络可以提高我们对 m6A 修饰在 LUAD 进展中的认识。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a217/10401877/5c1a60e3724c/12890_2023_2545_Fig1_HTML.jpg

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