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以GPR37为中心的ceRNA网络促进肺腺癌的转移潜能:来自高通量测序的证据。

GPR37-centered ceRNA network contributes to metastatic potential in lung adenocarcinoma: Evidence from high-throughput sequencing.

作者信息

Chen Chuanhui, Wan Mengzhi, Peng Xiong, Zhang Qing, Liu Yu

机构信息

Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Nanchang University, Nanchang 330006, PR China.

Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Nanchang University, Nanchang 330006, PR China.

出版信息

Transl Oncol. 2024 Jan;39:101819. doi: 10.1016/j.tranon.2023.101819. Epub 2023 Nov 16.

Abstract

The competing endogenous RNA (ceRNA)-based profiling has been extensively studied in carcinogenesis of lung adenocarcinoma (LUAD), while it has seldomly been applied to investigate the metastatic potential of LUAD. This study aims to examine the function and in-depth mechanism of GPR37-centered ceRNA network in LUAD. Cancer tissues and adjacent normal tissues from three LUAD patients were collected for high-throughput sequencing to screen for differentially expressed genes. A PPI network was constructed to screen the key gene GPR37, followed by analysis for the functions and pathways. Clinical data from LUAD patients were integrated with gene expression data in TCGA-LUAD dataset for survival analysis. Based on the miRNAs targeting_GPR37 and lncRNAs targeting_miRNAs, a lncRNA-miRNA-mRNA ceRNA network was established. GPR37 was up-regulated in LUAD tissue samples, and it may be a key gene involved in LUAD progression. GPR37 in LUAD was mainly enriched in the mitosis-related pathways. High GPR37 expression corresponded to poor prognosis in LUAD patients. Meanwhile, GPR37 could be used as an independent factor to predict the prognosis in LUAD patients. LncRNA DLEU1, up-regulated in LUAD tissue samples, may competitively bind to miR-4458 to up-regulate the expression of the miR-4458 downstream target GPR37. DLEU1 was associated with poor prognosis and tumor metastasis in LUAD patients. Altogether, our findings reveal a novel ceRNA network of DLEU1/miR-4458/GPR37 in LUAD growth and metastasis.

摘要

基于竞争性内源性RNA(ceRNA)的分析在肺腺癌(LUAD)的致癌过程中已得到广泛研究,而很少被用于研究LUAD的转移潜能。本研究旨在探讨以GPR37为中心的ceRNA网络在LUAD中的功能及深入机制。收集3例LUAD患者的癌组织和癌旁正常组织进行高通量测序,以筛选差异表达基因。构建蛋白质-蛋白质相互作用(PPI)网络以筛选关键基因GPR37,随后分析其功能和通路。将LUAD患者的临床数据与TCGA-LUAD数据集中的基因表达数据整合进行生存分析。基于靶向GPR37的微小RNA(miRNA)和靶向miRNA的长链非编码RNA(lncRNA),建立lncRNA-miRNA-mRNA ceRNA网络。GPR37在LUAD组织样本中上调,可能是参与LUAD进展的关键基因。LUAD中的GPR37主要富集于有丝分裂相关通路。GPR37高表达与LUAD患者预后不良相关。同时,GPR37可作为预测LUAD患者预后的独立因素。LncRNA DLEU1在LUAD组织样本中上调,可能竞争性结合miR-4458以上调miR-4458下游靶标GPR37的表达。DLEU1与LUAD患者的预后不良和肿瘤转移相关。总之,我们的研究结果揭示了LUAD生长和转移中一个新的DLEU1/miR-4458/GPR37 ceRNA网络。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5f6/10656721/b9fdd3548908/gr1.jpg

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