Deubiquitinating enzyme MINDY1 is an independent risk factor for the maintenance of stemness and poor prognosis in liver cancer cells.
10.3760/cma.j.cn501113-20230130-00028
- Author:
Bo Lin XIA
1
;
Ke Wei LIU
2
;
Hong Xia HUANG
3
;
Mei Mei SHEN
1
;
Bin WANG
2
;
Jian GAO
1
Author Information
1. Department of Gastroenterology, Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China.
2. Department of Gastroenterology, Chongqing Key Laboratory of Digestive Malignancies, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing 400042, China.
3. Daping Hospital, Army Medical University (Third Military Medical University), Chongqing 400042, China.
- Publication Type:Journal Article
- Keywords:
Deubiquitinase;
Liver cancer stem cells;
MINDY1
- MeSH:
Animals;
Mice;
Cell Line, Tumor;
Mice, Nude;
Liver Neoplasms/pathology*;
Prognosis;
Deubiquitinating Enzymes/metabolism*;
Neoplastic Stem Cells/pathology*;
Gene Expression Regulation, Neoplastic
- From:
Chinese Journal of Hepatology
2023;31(5):518-523
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To explore the key deubiquitinating enzymes that maintain the stemness of liver cancer stem cells and provide new ideas for targeted liver cancer therapy. Methods: The high-throughput CRISPR screening technology was used to screen the deubiquitinating enzymes that maintain the stemness of liver cancer stem cells. RT-qPCR and Western blot were used to analyze gene expression levels. Stemness of liver cancer cells was detected by spheroid-formation and soft agar colony formation assays. Tumor growth in nude mice was detected by subcutaneous tumor-bearing experiments. Bioinformatics and clinical samples were examined for the clinical significance of target genes. Results: MINDY1 was highly expressed in liver cancer stem cells. The expression of stem markers, the self-renewal ability of cells, and the growth of transplanted tumors were significantly reduced and inhibited after knocking out MINDY1, and its mechanism of action may be related to the regulation of the Wnt signaling pathway. The expression level of MINDY1 was higher in liver cancer tissues than that in adjacent tumors, which was closely related to tumor progression, and its high expression was an independent risk factor for a poor prognosis of liver cancer. Conclusion: The deubiquitinating enzyme MINDY1 promotes stemness in liver cancer cells and is one of the independent predictors of poor prognosis in liver cancer.
