Construction and Investigation of an LINC00284-Associated Regulatory Network in Serous Ovarian Carcinoma
Construction and Investigation of an LINC00284-Associated Regulatory Network in Serous Ovarian Carcinoma
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浆液性卵巢癌中 LINC00284 相关调控网络的构建和研究
DOI：
10.1155/2020/9696285
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发表时间：
2020-01-22
期刊：
影响因子：
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通讯作者：
Jia, Wei
中科院分区：
文献类型：
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作者：
Wang, Shasha;Zhang, Lu;Jia, Wei
与浆液性卵巢癌（SOC）相关的低生存率主要是由于缺乏早期发现和治疗的相关分子标志物。越来越多的实验证据表明，长链非编码RNA（lncRNA）参与了肿瘤的发生和发展，并提出了竞争性内源RNA（ceRNA）假说。因此，新的lncRNA和lncRNA相关网络的表征对于SOC的早期诊断和靶向治疗是至关重要的。与正常卵巢组织相比，在SOC中具有差异表达的lncRNA、mRNA和miRNA的数据从基因表达综合数据库（GEO）获得。关于lncRNA表达的数据和SOC中的临床数据从癌症基因组图谱（TCGA）获得。通过miRBase数据库预测lncRNA-miRNA相互作用。不同的在线工具，即，TargetScan、RNA 22、miRmap、microT、米兰达、StarBase和PicTar被合作地用于预测由miRNA靶向的mRNA。使用Cytoscape中的BiNGO插件和KOBAS 3.0进行功能和途径富集分析。使用qRT-PCR进一步验证经鉴定在SOC和健康输卵管组织之间以统计学显著性和不同水平表达的lncRNA、miRNA和mRNA。基于GEO数据库，发现与正常组织相比，SOC组织中共有4种lncRNA（LINC 00284、HAGLR、HCAT 158和BLACAT 1）和111种mRNA上调。发现LINC 00284在SOC中高度表达，与转录因子SOX 9的上调相关。基于TCGA数据库，LINC 00284高表达与不良预后相关，并且被证明是SOC患者的独立危险因素。qRT-PCR验证结果密切概括了上述生物信息学分析的表达谱和预后评分。通过生物功能分析发现LINC 00284相关的ceRNA网络与SOC致癌相关。总之，LINC 00284相关的ceRNA网络可以提供关于SOC起始和进展机制的有价值的信息。重要的是，LINC 00284被证明是SOC的新的潜在预后生物标志物。
The low survival rate associated with serous ovarian carcinoma (SOC) is largely due to the lack of relevant molecular markers for early detection and therapy. Increasing experimental evidence has demonstrated that long noncoding RNAs (lncRNAs) are involved in cancer initiation and development, and a competitive endogenous RNA (ceRNA) hypothesis has been formulated. Therefore, the characterization of new lncRNA and lncRNA-related networks is crucial for early diagnosis and targeted therapy of SOC. Data on lncRNAs, mRNAs, and miRNAs with differential expression in SOC, compared to normal ovarian tissue, were obtained from the Gene Expression Omnibus (GEO) database. Data on lncRNA expression and clinical data in SOC were obtained from The Cancer Genome Atlas (TCGA). lncRNA-miRNA interactions were predicted by the miRBase database. Different online tools, i.e., TargetScan, RNA22, miRmap, microT, miRanda, StarBase, and PicTar, were cooperatively utilized to predict the mRNAs targeted by miRNAs. The plugin of BiNGO in Cytoscape and KOBAS 3.0 were used to conduct the functional and pathway enrichment analyses. The lncRNA, miRNAs, and mRNAs identified to be expressed at statistically significant and different levels between SOC and healthy fallopian tube tissues were further validated using qRT-PCR. A total of 4 lncRNAs (LINC00284, HAGLR, HCAT158, and BLACAT1) and 111 mRNAs were found to be upregulated in SOC tissues compared to normal tissues, based on the GEO database. LINC00284 was found to be highly expressed in SOC, in association with the upregulation of the transcription factor SOX9. The high LINC00284 expression was associated with poor prognosis and proved to be an independent risk factor in patients with SOC, based on TCGA database. The qRT-PCR validation results closely recapitulated the expression profiles and prognostic scores of the aforementioned bioinformatic analyses. The LINC00284-related ceRNA network was found to be associated with SOC carcinogenesis by biofunctional analysis. In conclusion, the LINC00284-related ceRNA network may provide valuable information on the mechanisms of SOC initiation and progression. Importantly, LINC00284 proved to be a new potential prognostic biomarker for SOC.