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LINC00973-miRNA-mRNA ceRNA 调控网络及其在非小细胞肺癌进展中的潜在作用。

The Regulatory Network and Potential Role of LINC00973-miRNA-mRNA ceRNA in the Progression of Non-Small-Cell Lung Cancer.

机构信息

Department of Cardiothoracic Surgery, Taihe Hospital, Hubei University of Medicine, Shiyan, China.

Department of Oncology, Huanggang Central Hospital, Huanggang, China.

出版信息

Front Immunol. 2021 Jul 29;12:684807. doi: 10.3389/fimmu.2021.684807. eCollection 2021.

DOI:10.3389/fimmu.2021.684807
PMID:34394080
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8358408/
Abstract

BACKGROUND

The occurrence and development of cancer could be promoted by abnormally competing endogenous RNAs (ceRNA) network. This article aims to determine the prognostic biomarker of ceRNA for non-small-cell lung cancer (NSCLC) prognosis.

METHODS

The expression and clinical significance of LINC00973 in NSCLC tissues were analyzed the The Cancer Genome Atlas (TCGA), Gene Expression Profiling Interactive Analysis (GEPIA), lnCAR, and clinical samples in Taihe Hospital. The biological functions and signaling pathways involved in target genes of ceRNA network were analyzed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Survival analysis, univariate and multivariate Cox regression analysis were used for prognostic-related mRNA.

RESULTS

Expression of LINC00973 was increased in NSCLC tissues. High expression of LINC00973 was associated with poor prognosis of NSCLC patients. There were 15 miRNA and 238 differential mRNA in the INC00973-miRNA-mRNA ceRNA network, involving cell migration, endothelial cell proliferation, tumor growth factor (TGF)-β, cellular senescence, phosphatidylinositol 3-hydroxy kinase (PI3K)-Akt, Hippo, Rap1, mitogen-activated protein kinase (MAPK), cell cycle signaling pathway, etc. The expression levels of RTKN2, NFIX, PTX3, BMP2 and LOXL2 were independent risk factors for the poor prognosis of NSCLC patients.

CONCLUSIONS

LINC00973-miRNA-mRNA ceRNA network might be the basis for determining pivotal post-translational regulatory mechanisms in the progression of NSCLC. BMP2, LOXL2, NFIX, PTX3 and RTKN2 might be valuable prognostic markers and potential therapeutic targets.

摘要

背景

异常竞争内源性 RNA（ceRNA）网络可促进癌症的发生和发展。本文旨在确定 ceRNA 对非小细胞肺癌（NSCLC）预后的预测生物标志物。

方法

分析了 NSCLC 组织中 LINC00973 的表达及其在 TCGA、GEPIA、lnCAR 和泰禾医院临床样本中的临床意义。通过基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析 ceRNA 网络靶基因涉及的生物学功能和信号通路。采用生存分析、单因素和多因素 Cox 回归分析与预后相关的 mRNA。

结果

LINC00973 在 NSCLC 组织中表达上调。LINC00973 高表达与 NSCLC 患者预后不良相关。在 LINC00973-miRNA-mRNA ceRNA 网络中，有 15 个 miRNA 和 238 个差异表达 mRNA，涉及细胞迁移、内皮细胞增殖、肿瘤生长因子（TGF）-β、细胞衰老、磷脂酰肌醇 3-羟激酶（PI3K）-Akt、 Hippo、Rap1、丝裂原激活蛋白激酶（MAPK）、细胞周期信号通路等。RTKN2、NFIX、PTX3、BMP2 和 LOXL2 的表达水平是 NSCLC 患者预后不良的独立危险因素。

结论

LINC00973-miRNA-mRNA ceRNA 网络可能是确定 NSCLC 进展中关键翻译后调控机制的基础。BMP2、LOXL2、NFIX、PTX3 和 RTKN2 可能是有价值的预后标志物和潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/51fa/8358408/1b763a052061/fimmu-12-684807-g009.jpg
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