SLC50A1 inhibits the doxorubicin sensitivity in hepatocellular carcinoma cells through regulating the tumor glycolysis

Ganggang Wang; Wenzhi Jin; Lianmei Zhang; Meiyuan Dong; Xin Zhang; Zhijie Zhou; Xiaoliang Wang

doi:10.1038/s41420-024-02261-3

SLC50A1 inhibits the doxorubicin sensitivity in hepatocellular carcinoma cells through regulating the tumor glycolysis

Cell Death Discov. 2024 Dec 18;10(1):495. doi: 10.1038/s41420-024-02261-3.

Authors

Ganggang Wang^#¹, Wenzhi Jin^#¹, Lianmei Zhang^#¹, Meiyuan Dong^#^{2

3}, Xin Zhang¹, Zhijie Zhou¹, Xiaoliang Wang⁴

Affiliations

¹ Department of Hepatobiliary Surgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China.
² Graduate School of Hebei Medical University, Shijiazhuang, People's Republic of China.
³ Department of Endocrinology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China.
⁴ Department of Hepatobiliary Surgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China. Xiaoliangwang2018@163.com.

^# Contributed equally.

Abstract

Metabolic reprogramming has been found to be closely associated with the occurrence and development of hepatocellular carcinoma (HCC). The relationship between SLC50A1, a member of the SLC family involved in glucose transmembrane transport, and HCC remains unclear. This study aims to investigate the function and underlying mechanisms of SLC50A1 in the occurrence and progression of HCC. Based on bioinformatics analysis and clinical sample testing, we observed a significant upregulation of SLC50A1 in HCC, which is correlated with unfavorable prognosis in HCC patients. Additionally, there is a noticeable correlation between the expressions of SLC50A1 and METTL3. Further in vitro and in vivo experiments confirmed that SLC50A1 can regulate cellular glycolysis and the cell cycle, thereby promoting the proliferation of HCC cells while reducing apoptosis. Moreover, our findings indicate that SLC50A1 enhances resistance of HCC cells to DOX and 2-DG. Furthermore, we discovered that the m6A methyltransferase METTL3 mediates the methylation modification of SLC50A1. The recognition and binding of the modified SLC50A1 by IGF2BP2 subsequently promote its stability and translational expression. Consequently, our research identifies the METTL3/SLC50A1 axis as a novel therapeutic target in the context of HCC.