Department of Oncology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei province, China.
Department of Oncology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei province, China.
Biochem Biophys Res Commun. 2019 Dec 3;520(2):333-340. doi: 10.1016/j.bbrc.2019.09.137. Epub 2019 Oct 8.
Aberrant expression of long non-coding RNAs (lncRNAs) has been observed in hepatocellular carcinoma (HCC) and confirmed to participate in the initiation and progression of HCC. In the present study, we identified a novel functional lncRNA, hedgehog-interacting protein antisense RNA 1 (HHIP-AS1). The expression levels of HHIP-AS1 were significantly decreased in HCC tissues. Downregulation of HHIP-AS1 expression correlated with larger tumor size, metastasis, and advanced TNM stage, and also predicted worse overall survival rate of HCC patients. Through performing overexpression and knockdown experiments, the biological function of HHIP-AS1 was identified to suppress HCC cell proliferation, migration and invasion, while promote apoptosis. Further investigation showed that HHIP-AS1 interacted with and positively regulated the stability of HHIP mRNA in a HuR-dependent manner. HHIP-AS1 exerted its suppressive effects through HHIP. Taken together, our findings demonstrate that HHIP-AS1 represses HCC progression by promoting HHIP expression, and indicate that the use of HHIP-AS1 may offer a promising treatment for HCC patients.
长链非编码 RNA（lncRNAs）的异常表达已在肝细胞癌（HCC）中观察到，并证实其参与了 HCC 的发生和发展。在本研究中，我们鉴定了一种新型功能性 lncRNA，即 hedgehog-interacting protein antisense RNA 1（HHIP-AS1）。HHIP-AS1 在 HCC 组织中的表达水平显著降低。HHIP-AS1 表达下调与肿瘤体积较大、转移和较晚的 TNM 分期相关，并且也预示着 HCC 患者的总体生存率较差。通过进行过表达和敲低实验，鉴定了 HHIP-AS1 的生物学功能，即抑制 HCC 细胞增殖、迁移和侵袭，同时促进细胞凋亡。进一步的研究表明，HHIP-AS1 通过 HuR 依赖性方式与 HHIP mRNA 相互作用并正向调节其稳定性。HHIP-AS1 通过 HHIP 发挥其抑制作用。总之，我们的研究结果表明 HHIP-AS1 通过促进 HHIP 表达抑制 HCC 进展，并表明 HHIP-AS1 的应用可能为 HCC 患者提供一种有前途的治疗方法。
