Oncology Institute, The Affiliated Hospital of Jiangnan University, Wuxi, 214062, China.
Department of Malaria Control, Jiangsu Institute of Parasitic Diseases, Wuxi, 214064, China.
Biochem Biophys Res Commun. 2020 Dec 17;533(4):1039-1047. doi: 10.1016/j.bbrc.2020.09.115. Epub 2020 Oct 1.
Hepatocellular carcinoma (HCC) is the most prevalent type of liver cancer. In this study, we aimed to explore the role and mechanism of lncRNA ST8SIA6-AS1 in HCC. We found that ST8SIA6-AS1 was upregulated in HCC tissues and associated with poorer overall survival of HCC patients from TCGA. Moreover, ST8SIA6-AS1 was highly expressed in HCC in-house tissues and cells, and ST8SIA6-AS1 upregulation was related to aggressive tumor phenotypes and the poor overall survival of HCC patients. Downregulation of ST8SIA6-AS1 suppressed HCC cell proliferation, migration and invasion in vitro and restrained HCC tumorigenesis in vivo. In terms of mechanism, ST8SIA6-AS1 regulated melanoma-associated antigen (MAGE)-A3 (MAGEA3) and DDB1-and Cul4-associated factor 4-like 2 (DCAF4L2) expression, and rescue experiments verified that ST8SIA6-AS1 played a protumorigenic role in HCC via the regulation of MAGEA3 and DCAF4L2. ST8SIA6-AS1 partly directly bound to miR-129-5p and functioned as a competing endogenous RNA (ceRNA), subsequently facilitating the expression of the miR-129-5p target gene DCAF4L2 to play its role in HCC. In summary, our results identified ST8SIA6-AS1 as an oncogenic lncRNA predicting poor clinical outcomes of patients with HCC. These findings suggest that ST8SIA6-AS1 is a potential therapeutic target for HCC.
肝细胞癌(HCC)是最常见的肝癌类型。在本研究中,我们旨在探讨长链非编码 RNA ST8SIA6-AS1 在 HCC 中的作用和机制。我们发现 ST8SIA6-AS1 在 HCC 组织中上调,并与 TCGA 中 HCC 患者的总生存期较差相关。此外,ST8SIA6-AS1 在 HCC 组织和细胞中高表达,ST8SIA6-AS1 上调与侵袭性肿瘤表型和 HCC 患者的总生存期较差相关。下调 ST8SIA6-AS1 抑制 HCC 细胞的增殖、迁移和侵袭,并在体内抑制 HCC 肿瘤发生。就机制而言,ST8SIA6-AS1 调节黑色素瘤相关抗原(MAGE)-A3(MAGEA3)和 DDB1 和 Cul4 相关因子 4 样 2(DCAF4L2)的表达,并且挽救实验验证了 ST8SIA6-AS1 通过调节 MAGEA3 和 DCAF4L2 在 HCC 中发挥促肿瘤作用。ST8SIA6-AS1 部分直接与 miR-129-5p 结合,并作为竞争内源性 RNA(ceRNA)起作用,随后促进 miR-129-5p 靶基因 DCAF4L2 的表达,从而在 HCC 中发挥其作用。总之,我们的研究结果确定 ST8SIA6-AS1 是一种预测 HCC 患者临床结局不良的致癌 lncRNA。这些发现表明 ST8SIA6-AS1 是 HCC 的潜在治疗靶点。