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长链非编码 RNA ST8SIA6-AS1 通过调节 MAGEA3 和 DCAF4L2 的表达促进肝癌进展。

LncRNA ST8SIA6-AS1 promotes hepatocellular carcinoma progression by regulating MAGEA3 and DCAF4L2 expression.

机构信息

Oncology Institute, The Affiliated Hospital of Jiangnan University, Wuxi, 214062, China.

Department of Malaria Control, Jiangsu Institute of Parasitic Diseases, Wuxi, 214064, China.

出版信息

Biochem Biophys Res Commun. 2020 Dec 17;533(4):1039-1047. doi: 10.1016/j.bbrc.2020.09.115. Epub 2020 Oct 1.

Abstract

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.

摘要

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。

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