Identification of LINC02310 as an enhancer in lung adenocarcinoma and investigation of its regulatory network via comprehensive analyses.
Identification of LINC02310 as an enhancer in lung adenocarcinoma and investigation of its regulatory network via comprehensive analyses.
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DOI：
10.1186/s12920-020-00834-6
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发表时间：
2020-12-11
影响因子：
2.7
通讯作者：
Duan C
中科院分区：
文献类型：
--
作者：
Zhao W;Wang J;Luo Q;Peng W;Li B;Wang L;Zhang C;Duan C
肺腺癌（LADC）是非小细胞肺癌的一个主要亚型，是死亡率最高的肺癌之一。据报道，越来越多的长链非编码rna （lncrna）与LADC的发生和进展有关。因此，在lncrna中寻找新的LADC预后生物标志物是必要和合理的。通过差异表达分析、生存分析、PCR实验和临床特征分析，筛选出与LADC显著相关的LncRNA。CCK-8实验和菌落验证了其在LADC中的作用。此外，通过竞争性内源RNA （ceRNA）调控网络构建、富集分析和蛋白-蛋白相互作用（PPI）网络构建来研究所选LncRNA的下游调控网络。共有2431个差异表达LncRNAs （DELncRNAs）和2227个差异表达mrna （DEmRNAs）来自The Cancer Genome Atlas数据库。生存分析结果显示，lnc-YARS2-5、lnc-NPR3-2和LINC02310与总生存显著相关。它们的过度表达表明预后不良。PCR实验和临床特征分析表明，LINC02310与tnm分期和t分期有显著相关性。CCK-8实验和集落形成实验表明LINC02310在LADC中具有增强子的作用。此外，预测了LINC02310的3个靶向mirna和414个下游demrna。然后在405个基因本体术语和11个京都基因和基因组百科全书路径中富集下游demrna，揭示了它们的潜在功能和机制。PPI网络显示了下游demrna之间的相互作用。本研究证实LINC02310是LADC的增强子，并对其下游调控网络进行了全面分析，这可能有利于LADC的预后和治疗。
Lung adenocarcinoma (LADC) is a major subtype of non-small cell lung cancer and has one of the highest mortality rates. An increasing number of long non-coding RNAs (LncRNAs) were reported to be associated with the occurrence and progression of LADC. Thus, it is necessary and reasonable to find new prognostic biomarkers for LADC among LncRNAs. Differential expression analysis, survival analysis, PCR experiments and clinical feature analysis were performed to screen out the LncRNA which was significantly related to LADC. Its role in LADC was verified by CCK-8 assay and colony. Furthermore, competing endogenous RNA (ceRNA) regulatory network construction, enrichment analysis and protein–protein interaction (PPI) network construction were performed to investigate the downstream regulatory network of the selected LncRNA. A total of 2431 differentially expressed LncRNAs (DELncRNAs) and 2227 differentially expressed mRNAs (DEmRNAs) were from The Cancer Genome Atlas database. Survival analysis results indicated that lnc-YARS2-5, lnc-NPR3-2 and LINC02310 were significantly related to overall survival. Their overexpression indicated poor prognostic. PCR experiments and clinical feature analysis suggested that LINC02310 was significantly correlated with TNM-stage and T-stage. CCK-8 assay and colony formation assay demonstrated that LINC02310 acted as an enhancer in LADC. In addition, 3 targeted miRNAs of LINC02310 and 414 downstream DEmRNAs were predicted. The downstream DEmRNAs were then enriched in 405 Gene Ontology terms and 11 Kyoto Encyclopedia of Genes and Genomes pathways, which revealed their potential functions and mechanisms. The PPI network showed the interactions among the downstream DEmRNAs. This study verified LINC02310 as an enhancer in LADC and performed comprehensive analyses on its downstream regulatory network, which might benefit LADC prognoses and therapies.
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