General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China; Department of Biliary-Hepatic Surgery, The Affiliated Hospital of Guizhou Medical University, Guizhou, China.
Department of Biliary-Hepatic Surgery, The Affiliated Hospital of Guizhou Medical University, Guizhou, China.
Biomed Pharmacother. 2018 Apr;100:374-380. doi: 10.1016/j.biopha.2018.02.023. Epub 2018 Feb 16.
Hepatocellular carcinoma (HCC) is one of the most common tumors, so far, there still aren't good therapeutic methods. Looking for new targets makes a top priority. In this study, we found a OCT4 pseudogene, POU5F1B was significantly upregulated in HCC cells and tissues, patients with high POU5F1B had shorter survival time compared to patients with low POU5F1B expression. POU5F1B overexpression promoted HCC proliferation, while its knockdown inhibited HCC proliferation determined by MTT assay, soft agar growth assay, BrdU incorporation assay, and cell cycle assay. Mechanism analysis suggested POU5F1B could activate AKT, AKT inhibition in HCC cells with POU5F1B overexpression significantly inhibited cell proliferation compared to cells only with POU5F1B overexpression, suggesting POU5F1B promoted HCC proliferation by activating AKT. Finally, we analyzed the relationship between POU5F1B expression and AKT activity in HCC tissues, and found POU5F1B expression was positive correlated with activated AKT. Taken together, our findings suggested POU5F1B promoted HCC proliferation by activating AKT, and provided a new target for HCC therapy.
肝细胞癌 (HCC) 是最常见的肿瘤之一，到目前为止，仍然没有很好的治疗方法。寻找新的靶点是当务之急。在这项研究中，我们发现了一个 OCT4 假基因，POU5F1B 在 HCC 细胞和组织中显著上调，POU5F1B 高表达的患者与 POU5F1B 低表达的患者相比，生存时间更短。POU5F1B 过表达促进 HCC 增殖，而 MTT 测定、软琼脂生长测定、BrdU 掺入测定和细胞周期测定表明其敲低抑制 HCC 增殖。机制分析表明 POU5F1B 可以激活 AKT，在 POU5F1B 过表达的 HCC 细胞中抑制 AKT，与仅过表达 POU5F1B 的细胞相比，细胞增殖明显受到抑制，表明 POU5F1B 通过激活 AKT 促进 HCC 增殖。最后，我们分析了 HCC 组织中 POU5F1B 表达与 AKT 活性的关系，发现 POU5F1B 表达与激活的 AKT 呈正相关。综上所述，我们的研究结果表明，POU5F1B 通过激活 AKT 促进 HCC 增殖，为 HCC 的治疗提供了一个新的靶点。
