PES1 is transcriptionally regulated by BRD4 and promotes cell proliferation and glycolysis in hepatocellular carcinoma

被引:31
作者
Fan, Ping [1 ]
Wang, Bo [2 ]
Meng, Zibo [2 ]
Zhao, Jingyuan [2 ]
Jin, Xin [1 ]
机构
[1] Huazhong Univ Sci & Technol, Union Hosp, Dept Digest Surg Oncol, Tongji Med Coll, Wuhan 430022, Hubei, Peoples R China
[2] Huazhong Univ Sci & Technol, Union Hosp, Dept Pancreat Surg, Tongji Med Coll, Wuhan 430022, Hubei, Peoples R China
关键词
Pescadillo homologue 1 (PES1); Hepatocellular carcinoma (HCC); Cell proliferation; Aerobic glycolysis; Bromodomain-containing protein 4 (BRD4); PANCREATIC-CANCER; GEMCITABINE RESISTANCE; RIBOSOME BIOGENESIS; UP-REGULATION; C-MYC; EXPRESSION; METASTASIS; ACTIVATION; GROWTH; BETA;
D O I
10.1016/j.biocel.2018.08.014
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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-contabling 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.
引用
收藏
页码:1 / 8
页数:8
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