Yang Li-Na, Ning Zhou-Yu, Wang Lai, Yan Xia, Meng Zhi-Qiang
Cancer Institute, Fudan University Shanghai Cancer Center Shanghai, China.
Deparment of Integrative Oncology, Fudan University Shanghai Cancer Center Shanghai 200032, China.
Am J Cancer Res. 2019 Aug 1;9(8):1607-1621. eCollection 2019.
Heat shock factors (HSFs) are essential for all organisms to survive exposures to acute stress. Recent years have witnessed the progress in uncovering the importance of HSFs in cancer cell oncogenesis, progression and metastasis. However, their roles in hepatocellular carcinoma (HCC) proliferation and the underlying mechanism have seldom been discussed. The present study aims to uncover the two important HSFs members HSF1 and HSF2 in hepatocellular carcinoma (HCC). By using the Cancer Genome Atlas (TCGA) dataset analysis, we investigated the prognosis value of HSF1 and HSF2 in HCC and identified HSF2 as a prediction factor of overall survival of HCC. cell line studies demonstrated that silencing HSF2 expression could decrease the proliferation in HCC cells. In depth mechanism analysis demonstrated that HSF2 promoted cell proliferation via positive regulation of aerobic glycolysis, and HSF2 interacted with euchromatic histone lysine methyltransferase 2 (EHMT2) to epigenetically silence fructose-bisphosphatase 1 (FBP1), which is a tumor suppressor and negative regulator of aerobic glycolysis in HCC. HSF2 expression indicated unfavorable prognosis of HCC patients and it could regulate aerobic glycolysis by suppression of FBP1 to support uncontrolled proliferation of HCC cells.
热休克因子（HSFs）对于所有生物体在急性应激暴露下存活至关重要。近年来，人们在揭示HSFs在癌细胞发生、进展和转移中的重要性方面取得了进展。然而，它们在肝细胞癌（HCC）增殖中的作用及其潜在机制很少被讨论。本研究旨在揭示肝细胞癌（HCC）中两个重要的HSF成员HSF1和HSF2。通过使用癌症基因组图谱（TCGA）数据集分析，我们研究了HSF1和HSF2在HCC中的预后价值，并确定HSF2为HCC总体生存的预测因子。细胞系研究表明，沉默HSF2表达可降低HCC细胞的增殖。深入的机制分析表明，HSF2通过对有氧糖酵解的正向调节促进细胞增殖，并且HSF2与常染色质组蛋白赖氨酸甲基转移酶2（EHMT2）相互作用，在表观遗传上使果糖二磷酸酶1（FBP1）沉默，FBP1是HCC中一种肿瘤抑制因子和有氧糖酵解的负调节因子。HSF2表达表明HCC患者预后不良，并且它可通过抑制FBP1来调节有氧糖酵解，以支持HCC细胞的不受控制增殖。
