Hypoxia-induced USP22 affects the malignant biological behavior of esophageal squamous cell carcinoma by regulating HIF-1α
- VernacularTitle:低氧诱导下USP22通过调控HIF-1α影响食管鳞状细胞癌的恶性生物学行为
- Author:
Yinghua HUANG
1
;
Dengyun MA
2
;
Yuhao QI
3
;
Shenghai WANG
1
;
Shengmei LI
4
;
Jun LI
3
,
5
Author Information
1. Department of Pathology and Pathophysiology, Medical College of Qinghai University, Xining, 810001, P. R. China
2. Department of Pathology, Qinghai Red Cross Hospital, Xining, 810000, P. R. China
3. Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, P. R. China
4. Department of Medical Laboratory Medicine, Qinghai Red Cross Hospital, Xining, 810000, P. R. China
5. Department of Thoracic Surgery, Qinghai Red Cross Hospital, Xining, 810000, P. R. China
- Publication Type:Journal Article
- Keywords:
Ubiquitin specific peptidase 22;
hypoxia-inducible factor-1α;
esophageal squamous cell carcinoma;
tumor microenvironment;
hypoxia;
biological behavior;
cell experiment
- From:
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery
2026;33(04):615-623
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of ubiquitin specific peptidase 22 (USP22) on the occurrence and development of esophageal squamous cell carcinoma (ESCC) under hypoxic conditions, and its regulatory relationship with hypoxia-inducible factor-1α (HIF-1α). Methods Western blotting and quantitative polymerase chain reaction were used to detect the differences in USP22 protein and mRNA expression between normal esophageal epithelial cells HEEC and ESCC cell lines KYSE30, KYSE150, EC9706, and TE-1 under normoxic (5% CO2, 20% O2, 75% N2) and hypoxic (5% CO2, 1% O2, 94% N2) conditions. By transfecting USP22 plasmid or siUSP22, ESCC cells were divided into a normoxia control group, a normoxia+USP22 group, a normoxia+siUSP22 group, a hypoxia control group, a hypoxia+USP22 group, and a hypoxia+siUSP22 group. The proliferation and migration abilities of cells in each group were detected. The expression of USP22 and HIF-1α under hypoxic conditions after up-regulating or down-regulating USP22 was detected, and their regulatory relationship was verified. The interaction between USP22 and HIF-1α was verified by co-immunoprecipitation (Co-IP) technique. Results Compared with HEEC cells, the expression of USP22 in ESCC cells was significantly increased (P<0.05). Up-regulation of USP22 expression promoted the proliferation and migration of ESCC cells, while silencing USP22 inhibited the proliferation and migration of ESCC cells (P<0.05). Under hypoxic conditions, the expression of USP22 and HIF-1α increased, and with the up-regulation of USP22 expression, the expression of HIF-1α also significantly increased (P<0.05). Co-IP experiment confirmed the binding between USP22 and HIF-1α. Conclusion Up-regulation of USP22 expression promotes the proliferation and migration of ESCC cells. Hypoxia microenvironment can induce the increase of USP22 expression in ESCC. USP22 may participate in the regulation of the occurrence and development of ESCC by directly binding to HIF-1α.
