Long noncoding RNA DLEU2 predicts a poor prognosis and enhances malignant properties in laryngeal squamous cell carcinoma through the miR-30c-5p/PIK3CD/Akt axis
Long noncoding RNA DLEU2 predicts a poor prognosis and enhances malignant properties in laryngeal squamous cell carcinoma through the miR-30c-5p/PIK3CD/Akt axis
复制标题
长非编码RNA DLEU2通过miR-30c-5p/PIK3CD/Akt轴预测喉鳞状细胞癌的不良预后并增强恶性特性
DOI：
10.1038/s41419-020-2581-2
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发表时间：
2020-06-18
影响因子：
9
通讯作者：
Xia, Ming
中科院分区：
文献类型：
--
作者：
Li, Xiaoming;Xu, Fenglei;Xia, Ming
长链非编码RNA（lncRNA）已被鉴定为多种人类癌症的潜在预后工具和治疗生物标志物。然而，影响喉鳞状细胞癌（LSCC）的关键lncRNA的功能作用和潜在机制在很大程度上是未知的。在这里，我们采用了一种新的子途径的策略，从癌症基因组图谱（TCGA）数据库的lncRNA-mRNA的配置文件的基础上，并确定lncRNA删除淋巴细胞白血病2（DLEU 2）作为一个致癌基因的发病机制LSCC。我们发现DLEU 2显着上调，并预测LSCC患者的临床结局较差。此外，DLEU 2的异位过表达在体内和体外均促进了LSCC细胞的增殖和迁移。从机制上讲，DLEU 2作为一种竞争性内源性RNA，通过吸收miR-30 c-5 p来调节PIK 3CD表达，随后激活Akt信号通路。作为DLEU 2的靶基因，PIK 3CD在喉鳞癌中也表达上调，并可预测预后不良。总之，我们发现新的LSCC相关基因DLEU 2通过miR-30 c-5 p/PIK 3CD/Akt轴增强LSCC的恶性特性。DLEU 2及其靶向的miR-30 c-5 p/PIK 3 CD/Akt轴可能是LSCC有价值的预后生物标志物和治疗靶点。
Long noncoding RNAs (lncRNAs) have been identified as potential prognostic tools and therapeutic biomarkers for a variety of human cancers. However, the functional roles and underlying mechanisms of key lncRNAs affecting laryngeal squamous cell carcinomas (LSCCs) are largely unknown. Here, we adopted a novel subpathway strategy based on the lncRNA-mRNA profiles from the Cancer Genome Atlas (TCGA) database and identified the lncRNA deleted in lymphocytic leukemia 2 (DLEU2) as an oncogene in the pathogenesis of LSCCs. We found that DLEU2 was significantly upregulated and predicted poor clinical outcomes in LSCC patients. In addition, ectopic overexpression of DLEU2 promoted the proliferation and migration of LSCC cells both in vivo and in vitro. Mechanistically, DLEU2 served as a competing endogenous RNA to regulate PIK3CD expression by sponging miR-30c-5p and subsequently activated the Akt signaling pathway. As a target gene of DLEU2, PIK3CD was also upregulated and could predict a poor prognosis in LSCC patients. In conclusion, we found that the novel LSCC-related gene DLEU2 enhances the malignant properties of LSCCs via the miR-30c-5p/PIK3CD/Akt axis. DLEU2 and its targeted miR-30c-5p/PIK3CD/Akt axis may represent valuable prognostic biomarkers and therapeutic targets for LSCCs.