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Yanqing Li,1 Huining Tian,2 Haoge Luo,1 Jiaying Fu,1 Yan Jiao,3 Yang Li1 1Department of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, People’s Republic of China; 2College of Translational Medicine, The First Affiliated Hospital of Jilin University, Jilin University, Changchun, Jilin 130021, People’s Republic of China; 3Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, People’s Republic of ChinaCorrespondence: Yang LiDepartment of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, People’s Republic of ChinaTel +86 185 4311 2059Fax +86 431 8561 9101Email ygli136@163.comPurpose: Ovarian cancer (OC) has the highest mortality among gynecological malignancies. Therefore, it is urgent to explore prognostic biomarkers to improve the survival of OC patients. One of the most prominent metabolic characteristics of cancer is effective glycolysis. Hexokinase 1 (HK1), as the first rate-limiting enzyme in glycolysis, is closely related to cancer progression. However, the role of HK1 in OC remains unclear.Materials and Methods: The Cancer Genome Atlas (TCGA) database was used to detect the expression of HK1 in OC patients. The chi-squared test was performed to examine the correlations between HK1 and patients’ clinical characteristics. Survival analyses were undertaken to determine the relationship between HK1 and patient survival, while the univariate/multivariate Cox model was used to evaluate the role of HK1 in patient prognosis. Gene Set Enrichment Analysis (GSEA) was performed to ascertain the related signaling pathways of HK1. RT-qPCR was implemented to validate the mRNA expression of HK1 in OC cells. MTT was used to detect cell viability after adding 2DG and knocking down HK1 in OC cells. HK1 protein expression was examined by Western blotting. Glucose uptake, lactate production, and ATP assays were undertaken following knockdown of HK1 in OC cells. Colony formation assays were performed to determine OC cell proliferation after HK1 knockdown. Transwell and wound healing assays were carried out to detect the invasion and migration of OC cells after HK1 knockdown.Results: We found that HK1 expression was increased in OC tissues and cells, and HK1 was related to the clinical characteristics of OC patients. Survival analysis revealed that OC patients in the HK1 overexpression group had poor survival. Moreover, univariant/multivariate analyses showed that HK1 may be an independent biomarker for the poor prognosis of OC patients. OC cell viability and proliferation decreased after knockdown of HK1. Consistently, glucose uptake, lactic acid production, ATP production, invasion, and migration were also decreased. Finally, GSEA enrichment analysis and Western blotting showed that HK1 was involved in MAPK/ERK signaling.Conclusion: HK1 may be a biomarker for the poor prognosis of OC patients and a potential therapeutic target.Keywords: HK1, ovarian cancer, prognosis, glycolysis

Huining Tian,1 Xiaoyu Zhu,2 You Lv,1 Yan Jiao,3 Guixia Wang1 1Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun 130021, Jilin, People’s Republic of China; 2Department of Nephrology, The First Hospital of Jilin University, Changchun 130021, Jilin, People’s Republic of China; 3Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, Changchun 130021, Jilin, People’s Republic of ChinaCorrespondence: Guixia WangDepartment of Endocrinology and Metabolism, The First Hospital of Jilin University, 71 Xinmin Street, Chaoyang District, Changchun 130021, Jilin, People’s Republic of ChinaTel +86 158 0438 1103Fax +86 431 8878 6259Email gwang168@jlu.edu.cnYan JiaoDepartment of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jilin University, 71 Xinmin Street, Chaoyang District, Changchun 130021, Jilin, People’s Republic of ChinaTel/ Fax +86 13843101157Email lagelangri1@126.comAbstract: Hepatocellular carcinoma (HCC) is a tumor that exhibits glucometabolic reprogramming, with a high incidence and poor prognosis. Usually, HCC is not discovered until an advanced stage. Sorafenib is almost the only drug that is effective at treating advanced HCC, and promising metabolism-related therapeutic targets of HCC are urgently needed. The “Warburg effect” illustrates that tumor cells tend to choose aerobic glycolysis over oxidative phosphorylation (OXPHOS), which is closely related to the features of the tumor microenvironment (TME). The HCC microenvironment consists of hypoxia, acidosis and immune suppression, and contributes to tumor glycolysis. In turn, the glycolysis of the tumor aggravates hypoxia, acidosis and immune suppression, and leads to tumor proliferation, angiogenesis, epithelial–mesenchymal transition (EMT), invasion and metastasis. In 2017, a mechanism underlying the effects of gluconeogenesis on inhibiting glycolysis and blockading HCC progression was proposed. Treating HCC by increasing gluconeogenesis has attracted increasing attention from scientists, but few articles have summarized it. In this review, we discuss the mechanisms associated with the TME, glycolysis and gluconeogenesis and the current treatments for HCC. We believe that a treatment combination of sorafenib with TME improvement and/or anti-Warburg therapies will set the trend of advanced HCC therapy in the future.Keywords: hepatocellular carcinoma, tumor microenvironment, glycolysis, gluconeogenesis, Warburg effect