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整合分析鉴定出口腔癌中的致癌长非编码 RNA DUXAP8。

Integrative profiling analysis identifies the oncogenic long noncoding RNA DUXAP8 in oral cancer.

机构信息

Department of Stomatology, affiliated Jining First People's Hospital of Jining Medical University, Jining.

Department of Stomatology, Guangzhou Hospital of Integrated Traditional and Western Medicine, Guangzhou, People's Republic of China.

出版信息

Anticancer Drugs. 2020 Sep;31(8):792-798. doi: 10.1097/CAD.0000000000000936.

DOI:10.1097/CAD.0000000000000936
PMID:32304409
Abstract

A growing number of studies have revealed the critical roles of long noncoding RNAs (lncRNAs) in the tumorigenesis and cancer progression. Recently, next-generation sequencing technologies combined with bioinformatic have demonstrated that a great number of dysregulated lncRNAs are associated with diverse cancers. However, lots of lncRNAs' function and their underlying molecular mechanisms in oral carcinoma (OC) cancer remain unclear. In this study, we performed integrative lncRNA profiling analysis using the TCGA RNA sequencing data and gene microarray data from Gene Expression Omnibus to identify more OC associated lncRNAs. A total of 619 differentially expressed lncRNAs were identified between the five data sets, and only the double homeobox A pseudogene 8 (DUXAP8) was screened among the up-regulated lncRNAs in all the five groups. Meanwhile, univariate Cox regression analyses disclosed that some lncRNAs are associated with the outcome of OC patients, such as DUXAP8, LINC00152, MIR4435-2HG and LINC00582. Furthermore, we uncovered that silenced DUXAP8 expression exerted suppressive impact on the proliferation of OC cells through interacting with histone-lysine N-methyltransferase enzyme Enhancer of zeste homolog 2 (EZH2) and repressing KLF2 expression. In a word, we identified a lot of unreported OC associated lncRNAs, which may provide a useful resource of lncRNAs for other studies.

摘要

越来越多的研究揭示了长非编码 RNA(lncRNA)在肿瘤发生和癌症进展中的关键作用。最近,下一代测序技术与生物信息学相结合,表明大量失调的 lncRNA 与多种癌症有关。然而,许多 lncRNA 在口腔鳞状细胞癌(OC)中的功能及其潜在的分子机制仍不清楚。在这项研究中,我们使用 TCGA RNA 测序数据和基因表达谱数据来自基因表达综合分析 lncRNA 谱分析,以鉴定更多与 OC 相关的 lncRNA。在五个数据集中共鉴定出 619 个差异表达的 lncRNA,在所有五个组上调的 lncRNA 中仅筛选出双同源盒 A 假基因 8(DUXAP8)。同时,单变量 Cox 回归分析表明,一些 lncRNA 与 OC 患者的预后相关,如 DUXAP8、LINC00152、MIR4435-2HG 和 LINC00582。此外,我们发现沉默 DUXAP8 表达通过与组蛋白赖氨酸 N-甲基转移酶酶 Enhancer of zeste 同源物 2(EZH2)相互作用并抑制 KLF2 表达,对 OC 细胞的增殖产生抑制作用。总之,我们鉴定了许多未报道的 OC 相关 lncRNA,它们可能为其他研究提供有用的 lncRNA 资源。

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