Department of Oncological Surgery, The Second Hospital of Hebei Medical University, No. 215 Peace West Road, Shijiazhuang 050000, China.
The First Department of Surgery, Feixiang Central Hospital, Handan 057550, China.
Biochim Biophys Acta Mol Basis Dis. 2017 Jul;1863(7):1805-1816. doi: 10.1016/j.bbadis.2017.04.014. Epub 2017 Apr 18.
Long noncoding RNAs (lncRNAs) have been shown to play important roles in various cancers. However, the clinical significances and biological roles of lncRNAs in hepatocellular carcinoma (HCC) remain largely unknown. In this study, using online-available data sets and quantitative real-time PCR, we identified a novel lncRNA termed lncRNA-AWPPH, which is highly expressed in HCC tissues. Its upregulation is correlated with encapsulation incomplete, microvascular invasion, advanced TNM stage and BCLC stage. Cox proportional hazards regression analysis revealed that high lncRNA-AWPPH expression is an independent prognostic factor for poor recurrence-free and overall survival. Functional experiments showed that overexpression of lncRNA-AWPPH promotes HCC cell proliferation and migration in vitro, and tumor growth and metastasis in vivo. Conversely, depletion of lncRNA-AWPPH has opposite effects on HCC. Mechanistically, lncRNA-AWPPH interacts with YBX1, promotes YBX1-mediated activation of SNAIL1 translation, and upregulates SNAIL1 expression. Furthermore, lncRNA-AWPPH promotes YBX1-mediated activation of PIK3CA transcription, upregulates PIK3CA expression, and activates PI3K/AKT pathway. Depletion of YBX1 abolishes the effects of lncRNA-AWPPH on SNAIL1 and PIK3CA, and also the biological roles of lncRNA-AWPPH on HCC cells. In conclusion, this study identifies a novel lncRNA termed lncRNA-AWPPH which is highly expressed in HCC, indicates poor prognosis of HCC patients, and promotes HCC cell proliferation, migration, and in vivo tumor growth and metastasis via a novel regulatory mechanism of interacting with YBX1.
长链非编码 RNA（lncRNAs）已被证明在各种癌症中发挥重要作用。然而，lncRNAs 在肝细胞癌（HCC）中的临床意义和生物学作用在很大程度上仍然未知。在这项研究中，我们使用在线可用数据集和定量实时 PCR 鉴定了一种新的 lncRNA，称为 lncRNA-AWPPH，其在 HCC 组织中高度表达。其上调与包膜不完整、微血管侵犯、晚期 TNM 分期和 BCLC 分期相关。Cox 比例风险回归分析显示，高 lncRNA-AWPPH 表达是预后不良的无复发生存和总生存的独立预后因素。功能实验表明，lncRNA-AWPPH 的过表达促进 HCC 细胞在体外的增殖和迁移，并促进体内肿瘤的生长和转移。相反，lncRNA-AWPPH 的耗竭对 HCC 具有相反的作用。机制上，lncRNA-AWPPH 与 YBX1 相互作用，促进 YBX1 介导的 SNAIL1 翻译激活，并上调 SNAIL1 表达。此外，lncRNA-AWPPH 促进 YBX1 介导的 PIK3CA 转录激活，上调 PIK3CA 表达，并激活 PI3K/AKT 通路。YBX1 的耗竭消除了 lncRNA-AWPPH 对 SNAIL1 和 PIK3CA 的影响，以及 lncRNA-AWPPH 对 HCC 细胞的生物学作用。总之，本研究鉴定了一种新的 lncRNA，称为 lncRNA-AWPPH，其在 HCC 中高度表达，预示着 HCC 患者的预后不良，并通过与 YBX1 相互作用的新调节机制促进 HCC 细胞的增殖、迁移以及体内肿瘤的生长和转移。
