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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.
Cell Death & Disease ( IF 9 ) Pub Date : 2020-06-18 , DOI: 10.1038/s41419-020-2581-2
Xiaoming Li 1 , Fenglei Xu 1 , Qiu Meng 1 , Ningyue Gong 1 , Zhenxiao Teng 1 , Runtong Xu 1 , Miaoqing Zhao 2 , Ming Xia 1
Affiliation  

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.



中文翻译:

长链非编码 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。

长链非编码 RNA (lncRNA) 已被确定为各种人类癌症的潜在预后工具和治疗性生物标志物。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,我们采用了一种基于癌症基因组图谱 (TCGA) 数据库中 lncRNA-mRNA 谱的新型亚通路策略,并将淋巴细胞白血病 2 (DLEU2) 中缺失的 lncRNA 鉴定为 LSCC 发病机制中的致癌基因。我们发现 DLEU2 显着上调并预测 LSCC 患者的不良临床结果。此外,DLEU2 的异位过表达促进了 LSCC 细胞在体内和体外的增殖和迁移。机械地,DLEU2 作为竞争性内源性 RNA 通过海绵化 miR-30c-5p 调节 PIK3CD 表达,随后激活 Akt 信号通路。作为 DLEU2 的靶基因,PIK3CD 也被上调,可以预测 LSCC 患者的不良预后。总之,我们发现新的 LSCC 相关基因 DLEU2 通过 miR-30c-5p/PIK3CD/Akt 轴增强了 LSCC 的恶性特性。DLEU2 及其靶向 miR-30c-5p/PIK3CD/Akt 轴可能代表 LSCC 的有价值的预后生物标志物和治疗靶点。

更新日期:2020-06-18
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