Department of Interventional and Vascular, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, China.
Department of Interventional and Vascular, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, China.
Eur J Pharmacol. 2019 Apr 15;849:106-114. doi: 10.1016/j.ejphar.2019.01.049. Epub 2019 Jan 30.
Hepatocellular carcinoma (HCC), as the commonest type in liver cancer, is in urgent need for better treatment target due to its high mortality and poor prognosis. The involvement of angiogenesis in HCC has been identified by multiple studies, but the underlying mechanism remains unclear. Long non-coding RNAs (LncRNAs) have been reported to regulate numerous cancers, including HCC. LncRNA-OR3A4 has been reported to exert oncogenic and angiogenetic functions in gastric cancer, but its role in HCC hasn't been elucidated. Present study aimed to uncover the biological role of OR3A4 in tumor progression and angiogenesis in HCC. The upregulation of OR3A4 in HCC tissues and cell lines and its prognostic significance were first identified. Loss-of-function assays, including CCK-8, transwell and tube formation assay, validated OR3A4 as a promoter for HCC progression and angiogenesis. The association of OR3A4 and AGGF1 with HCC and poor prognosis was identified by qRT-PCR and Kaplan-Meier analysis. Western blotting and spearman's correlation curve verified the effect of OR3A4 on AGGF1 level and their positive association. Rescue assays revealed that OR3A4 promoted cancer progression and angiogenesis in HCC via AGGF1/akt/mTOR. Together, present study revealed OR3A4 as a novel prognostic target for HCC, which regulated tumor progression and angiogenesis through AGGF1/akt/mTOR pathway.
肝细胞癌（HCC）作为肝癌中最常见的类型，由于其高死亡率和预后不良，迫切需要更好的治疗靶点。多项研究已经证实血管生成参与了 HCC，但潜在机制尚不清楚。长链非编码 RNA（LncRNA）已被报道可调节多种癌症，包括 HCC。有研究报道 LncRNA-OR3A4 在胃癌中具有致癌和血管生成功能，但它在 HCC 中的作用尚未阐明。本研究旨在揭示 OR3A4 在 HCC 肿瘤进展和血管生成中的生物学作用。首先确定了 OR3A4 在 HCC 组织和细胞系中的上调及其预后意义。CCK-8、Transwell 和管形成试验等功能丧失试验验证了 OR3A4 是 HCC 进展和血管生成的促进因子。通过 qRT-PCR 和 Kaplan-Meier 分析确定了 OR3A4 与 AGGF1 与 HCC 和不良预后的关联。Western blot 和 spearman 相关曲线验证了 OR3A4 对 AGGF1 水平及其正相关的影响。挽救试验表明，OR3A4 通过 AGGF1/akt/mTOR 促进 HCC 中的肿瘤进展和血管生成。总之，本研究揭示了 OR3A4 是 HCC 的一个新的预后靶点，它通过 AGGF1/akt/mTOR 通路调节肿瘤进展和血管生成。
