The abnormal elevation of sulfiredoxin (Srx/SRXN1)—an antioxidant enzyme whose main function is to protect against oxidative stress—has been shown to be closely correlated with the progression of several types of cancer, including human cervical cancer. However, the molecular mechanism by which Srx promotes tumor progression, especially cancer metastasis in cervical cancer, has not been elucidated. Here, we show that Srx expression gradually increases during the progression of human cervical cancer and its expression level is closely correlated with lymph node metastasis. Our study also reveals a significant positive correlation between the expression of Srx and β-catenin in cervical cancer tissues. Loss-of-function studies demonstrate that Srx knockdown using a lentiviral vector-mediated specific shRNA decreases the migration and invasion capacity in HeLa (human papilloma virus 18 type cervical cancer cell line) and SiHa SiHa (cervical squamous cancer cell line). Notably, the exact opposite effects were observed in gain-of-function experiments in C-33A cells. Mechanistically, downregulation or upregulation of Srx leads to an altered expression of proteins associated with the Wnt/β-catenin signaling pathway. Furthermore, blockage of the Wnt/β-catenin signaling pathway contributed to attenuated Srx expression and resulted in significant inhibition of cell migration and invasion in cervical cancer cell lines. Combined, Srx might be an oncoprotein in cervical cancer, playing critical roles in activating the Wnt/β-catenin signaling pathway; it may therefore be a therapeutic target for cervical cancer.
Sulfiredoxin (Srx), a novel oxidative stress-induced antioxidant protein, has been reported to be expressed in several human tumour tissues. However, the expression and functions of Srx in cervical squamous cell carcinoma remain unknown. Here, we proved that expression of Srx was upregulated in cervical tissues as revealed by immunohistochemistry, and revealed a close correlation between the protein's expression and the expression level of one core epithelial-mesenchymal transition marker, E-cadherin. We demonstrated that Srx was overexpressed in cervical squamous cell carcinoma and its expression level was closely correlated with lymph node metastasis and invasion of cervical squamous cell carcinoma. Meanwhile, Srx expression was negatively correlated with E-cadherin expression. The remission time (tumour-free status after surgery) of the Srx strong staining group was significantly shorter than that of the Srx weak staining group. We silenced Srx by short hairpin RNA in HeLa and SiHa cells. Diminished Srx expression upregulated E-cadherin expression. The cell invasion and migration activity in the ShSrx group were obviously decreased in HeLa and SiHa cells. Moreover, Srx regulated the expression of the other marker of epithelial-mesenchymal transition, vimentin. In conclusion, the study suggested that Srx was highly expressed in cervical squamous cell carcinoma and may promote invasion and metastasis of cervical squamous cell carcinoma via regulating epithelial-mesenchymal transition.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.