Department of Digestive Surgical Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.
Int J Biochem Cell Biol. 2018 Nov;104:1-8. doi: 10.1016/j.biocel.2018.08.014. Epub 2018 Aug 29.
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. However, the mechanism underlying the tumorigenesis of HCC is still unclear. Improper recruitment of Pescadillo homologue 1 (PES1) can lead to tumorigenesis in multiple cancer types, such as gastric cancer and colon cancer. Here, we reported that PES1 was upregulated and associated with a poor prognosis in HCC specimens. Next, we found that PES1 promoted the growth of HCC in vivo and in vitro. Furthermore, we showed that the knockdown of PES1 decreased glycolysis via altering the gene expression of GLUT1, PKM2, ENO1, FBP1, and PCK1, which are related to glucose metabolism in HCC cells. Moreover, we demonstrated that PES1 is regulated by bromodomain-containing protein 4 (BRD4) and is partially responsible for modulating the antitumor effect of BET inhibitors in HCC. Taken together, our results suggest that PES1 plays an important role in promoting the proliferation of human liver cancer cells, suggesting that PES1 may be an ideal molecular target for HCC therapy.
肝细胞癌（HCC）是全球癌症相关死亡的主要原因之一。然而，HCC 的肿瘤发生机制尚不清楚。Pescadillo 同源物 1（PES1）的不当募集可导致多种癌症类型的肿瘤发生，如胃癌和结肠癌。在这里，我们报道 PES1 在 HCC 标本中上调，并与预后不良相关。接下来，我们发现 PES1 促进了 HCC 在体内和体外的生长。此外，我们表明 PES1 通过改变与 HCC 细胞葡萄糖代谢相关的 GLUT1、PKM2、ENO1、FBP1 和 PCK1 的基因表达来降低糖酵解。此外，我们证明 PES1 受溴结构域蛋白 4（BRD4）调节，并且部分负责调节 BET 抑制剂在 HCC 中的抗肿瘤作用。总之，我们的结果表明 PES1 在促进人肝癌细胞增殖中起重要作用，提示 PES1 可能是 HCC 治疗的理想分子靶标。
