Recently, Professor Zhou Ledu's team from the Department of Liver Surgery at Xiangya Hospital of Central South University (CSU) published an online paper titled “Targeting USP8 Inhibits O-GlcNAcylation of SLC7A11 to Promote Ferroptosis of Hepatocellular Carcinoma via Stabilization of OGT” in the internationally renowned journal Advanced Science. Professor Zhou Ledu, Professor Tao Yongguang and Associate Professor Xiao Liang are the co-corresponding authors of this paper. Tang Jianing, a postdoctoral fellow from the Department of Liver Surgery at Xiangya Hospital, is the first author. Xiangya Hospital is the affiliation of the first author and the corresponding author. Professor Liu Shuang from the Oncology Department and Professor Xiao Desheng from the Pathology Department provided strong support for the research.

Mechanism chart for the paper

Ferroptosis is a novel form of cell death driven by iron-dependent phospholipid peroxidation, and more and more evidence shows that ferroptosis plays an important role in tumors. Inducing ferroptosis, as a potential cancer treatment, has shown promising application value both as a monotherapy and in combination with other targeted drugs. Therefore, exploring the molecular mechanisms of ferroptosis is of great significance for tumor treatment.

In this research, researchers found through drug screening that USP8 small molecule inhibitors can significantly inhibit the activity of liver cancer cells. Mechanism studies have shown that USP8 deubiquitination modifies OGT protein to improve protein stability. The latter regulates SLC7A11, a key protein for ferroptosis, through glycosylation, thereby inhibiting ferroptosis in liver cancer. Targeting USP8 with small molecule inhibitors can induce ferroptosis in liver cancer, inhibit the growth of liver tumor, and provide potential effective therapeutic targets for new cancer drug development.

The Department of Liver Surgery at CSU Xiangya Hospital is one of the writers of the Guidelines for the Diagnosis and Treatment of Primary Liver Cancer issued by the National Health Commission, the affiliation of the Vice Chairman of the Liver Cancer Screening Special Committee of the National Cancer Center, among the first batch of liver cancer quality control units released by the National Cancer Center, the affiliation of the Chairman of the Liver Cancer Professional Committee of the Anticancer Association of Hunan Province, the affiliation of the leader of the Liver Surgery Group of Hunan Medical Association, and the leading unit of Hunan Liver Cancer Prevention and Treatment Alliance. It is the experimental base in Hunan Province for the standardized training program for primary liver cancer designated by the National Institute of Hospital Administration, National Health Commission.

(First Reviewer: Zhang Xu, Second Reviewer: Wang Xuan, Third Reviewer: Li Yin)

Source: Xiangya Hospital

Original article link: https://news.csu.edu.cn/info/1003/157183.htm