SUMO-Specific Peptidase 5 Promotes Oesophageal Squamous Cell Carcinoma Growth through the NF-κB-SLC1A3 Axis
Background: This study investigates the role of small ubiquitin-like modifier (SUMO)-specific peptidase 5 (SENP5), a key regulator of SUMOylation, in esophageal squamous cell carcinoma (ESCC), a lethal disease, and its underlying molecular mechanisms....
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
IMR Press
2025-01-01
|
| Series: | Frontiers in Bioscience-Landmark |
| Subjects: | |
| Online Access: | https://www.imrpress.com/journal/FBL/30/1/10.31083/FBL27047 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832586514137088000 |
|---|---|
| author | Chaoxiang Du Yunfan Hu Xinyu Yang Zhe Zhang Jianmin Gu Tao Zhang Renfeng Wang Shaoyuan Zhang Lijie Tan Guiping Yu |
| author_facet | Chaoxiang Du Yunfan Hu Xinyu Yang Zhe Zhang Jianmin Gu Tao Zhang Renfeng Wang Shaoyuan Zhang Lijie Tan Guiping Yu |
| author_sort | Chaoxiang Du |
| collection | DOAJ |
| description | Background: This study investigates the role of small ubiquitin-like modifier (SUMO)-specific peptidase 5 (SENP5), a key regulator of SUMOylation, in esophageal squamous cell carcinoma (ESCC), a lethal disease, and its underlying molecular mechanisms. Methods: Differentially expressed genes between ESCC mouse oesophageal cancer tissues and normal tissues were analysed via RNA-seq; among them, SENP5 expression was upregulated, and this gene was selected for further analysis. Immunohistochemistry and western blotting were then used to validate the increased protein level of SENP5 in both mouse and human ESCC samples. The Kaplan‒Meier method and multivariate analysis were used to analyse the relationship between SENP5 expression and ESCC prognosis. Stable SENP5-knockdown (KD) cell lines and conditional knockout (cKO) mice were established to verify the biological function of SENP5. Further RNA-seq comparisons between short hairpin SENP5 (shSENP5)- and short hairpin negative control (shNC)-transfected ESCC cell lines were conducted, and the nuclear factor kappa B (NF-κB)—SLC1A3 axis was identified through bioinformatics analysis. The correlation of SENP5 with signalling pathway components was validated via real-time quantitative PCR (qPCR), western blotting (WB), and immunoprecipitation. Results: Our study revealed that SENP5 was upregulated in human and mouse ESCC samples, and clinical data analysis revealed a correlation between high SENP5 expression and poor patient prognosis. SENP5 knockdown inhibited tumorigenesis and growth in vivo and suppressed the proliferation, migration, and invasion of ESCC cell lines in vitro. Our study also revealed that SENP5 knockdown enhanced the SUMO1-mediated SUMOylation of NF-kappa-B inhibitor alpha (IκBα), thereby inhibiting the activation of the NF-κB–SLC1A3 axis, which subsequently suppresses ESCC cell energy metabolism and impedes ESCC progression. Conclusions: Suppression of SENP5 slows the development of ESCC by inhibiting the NF-κB‒SLC1A3 axis through SUMO1-mediated SUMOylation of IκBα. Our research suggests that SENP5 could serve as a prognostic indicator and a target for therapeutic intervention for ESCC patients. |
| format | Article |
| id | doaj-art-7491a1fb75de45a1aa07569633f34b9d |
| institution | Kabale University |
| issn | 2768-6701 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | IMR Press |
| record_format | Article |
| series | Frontiers in Bioscience-Landmark |
| spelling | doaj-art-7491a1fb75de45a1aa07569633f34b9d2025-01-25T08:55:52ZengIMR PressFrontiers in Bioscience-Landmark2768-67012025-01-013012704710.31083/FBL27047S2768-6701(24)01589-2SUMO-Specific Peptidase 5 Promotes Oesophageal Squamous Cell Carcinoma Growth through the NF-κB-SLC1A3 AxisChaoxiang Du0Yunfan Hu1Xinyu Yang2Zhe Zhang3Jianmin Gu4Tao Zhang5Renfeng Wang6Shaoyuan Zhang7Lijie Tan8Guiping Yu9Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, 200032 Shanghai, ChinaDepartment of Thoracic Surgery, Zhongshan Hospital, Fudan University, 200032 Shanghai, ChinaDepartment of Thoracic Surgery, Zhongshan Hospital, Fudan University, 200032 Shanghai, ChinaDepartment of Cardiothoracic Surgery, The Affiliated Jiangyin Hospital of Nantong University, 214400 Jiangyin, Jiangsu, ChinaDepartment of Thoracic Surgery, Zhongshan Hospital, Fudan University, 200032 Shanghai, ChinaDepartment of Thoracic Surgery, Zhongshan Hospital (Xiamen), Fudan University, 361006 Xiamen, Fujian, ChinaDepartment of Thoracic Surgery, Zhongshan Hospital (Xiamen), Fudan University, 361006 Xiamen, Fujian, ChinaDepartment of Thoracic Surgery, Zhongshan Hospital, Fudan University, 200032 Shanghai, ChinaDepartment of Thoracic Surgery, Zhongshan Hospital, Fudan University, 200032 Shanghai, ChinaDepartment of Cardiothoracic Surgery, The Affiliated Jiangyin Hospital of Nantong University, 214400 Jiangyin, Jiangsu, ChinaBackground: This study investigates the role of small ubiquitin-like modifier (SUMO)-specific peptidase 5 (SENP5), a key regulator of SUMOylation, in esophageal squamous cell carcinoma (ESCC), a lethal disease, and its underlying molecular mechanisms. Methods: Differentially expressed genes between ESCC mouse oesophageal cancer tissues and normal tissues were analysed via RNA-seq; among them, SENP5 expression was upregulated, and this gene was selected for further analysis. Immunohistochemistry and western blotting were then used to validate the increased protein level of SENP5 in both mouse and human ESCC samples. The Kaplan‒Meier method and multivariate analysis were used to analyse the relationship between SENP5 expression and ESCC prognosis. Stable SENP5-knockdown (KD) cell lines and conditional knockout (cKO) mice were established to verify the biological function of SENP5. Further RNA-seq comparisons between short hairpin SENP5 (shSENP5)- and short hairpin negative control (shNC)-transfected ESCC cell lines were conducted, and the nuclear factor kappa B (NF-κB)—SLC1A3 axis was identified through bioinformatics analysis. The correlation of SENP5 with signalling pathway components was validated via real-time quantitative PCR (qPCR), western blotting (WB), and immunoprecipitation. Results: Our study revealed that SENP5 was upregulated in human and mouse ESCC samples, and clinical data analysis revealed a correlation between high SENP5 expression and poor patient prognosis. SENP5 knockdown inhibited tumorigenesis and growth in vivo and suppressed the proliferation, migration, and invasion of ESCC cell lines in vitro. Our study also revealed that SENP5 knockdown enhanced the SUMO1-mediated SUMOylation of NF-kappa-B inhibitor alpha (IκBα), thereby inhibiting the activation of the NF-κB–SLC1A3 axis, which subsequently suppresses ESCC cell energy metabolism and impedes ESCC progression. Conclusions: Suppression of SENP5 slows the development of ESCC by inhibiting the NF-κB‒SLC1A3 axis through SUMO1-mediated SUMOylation of IκBα. Our research suggests that SENP5 could serve as a prognostic indicator and a target for therapeutic intervention for ESCC patients.https://www.imrpress.com/journal/FBL/30/1/10.31083/FBL27047senp5oesophageal squamous cell carcinomaslc1a3nf-κb |
| spellingShingle | Chaoxiang Du Yunfan Hu Xinyu Yang Zhe Zhang Jianmin Gu Tao Zhang Renfeng Wang Shaoyuan Zhang Lijie Tan Guiping Yu SUMO-Specific Peptidase 5 Promotes Oesophageal Squamous Cell Carcinoma Growth through the NF-κB-SLC1A3 Axis Frontiers in Bioscience-Landmark senp5 oesophageal squamous cell carcinoma slc1a3 nf-κb |
| title | SUMO-Specific Peptidase 5 Promotes Oesophageal Squamous Cell Carcinoma Growth through the NF-κB-SLC1A3 Axis |
| title_full | SUMO-Specific Peptidase 5 Promotes Oesophageal Squamous Cell Carcinoma Growth through the NF-κB-SLC1A3 Axis |
| title_fullStr | SUMO-Specific Peptidase 5 Promotes Oesophageal Squamous Cell Carcinoma Growth through the NF-κB-SLC1A3 Axis |
| title_full_unstemmed | SUMO-Specific Peptidase 5 Promotes Oesophageal Squamous Cell Carcinoma Growth through the NF-κB-SLC1A3 Axis |
| title_short | SUMO-Specific Peptidase 5 Promotes Oesophageal Squamous Cell Carcinoma Growth through the NF-κB-SLC1A3 Axis |
| title_sort | sumo specific peptidase 5 promotes oesophageal squamous cell carcinoma growth through the nf κb slc1a3 axis |
| topic | senp5 oesophageal squamous cell carcinoma slc1a3 nf-κb |
| url | https://www.imrpress.com/journal/FBL/30/1/10.31083/FBL27047 |
| work_keys_str_mv | AT chaoxiangdu sumospecificpeptidase5promotesoesophagealsquamouscellcarcinomagrowththroughthenfkbslc1a3axis AT yunfanhu sumospecificpeptidase5promotesoesophagealsquamouscellcarcinomagrowththroughthenfkbslc1a3axis AT xinyuyang sumospecificpeptidase5promotesoesophagealsquamouscellcarcinomagrowththroughthenfkbslc1a3axis AT zhezhang sumospecificpeptidase5promotesoesophagealsquamouscellcarcinomagrowththroughthenfkbslc1a3axis AT jianmingu sumospecificpeptidase5promotesoesophagealsquamouscellcarcinomagrowththroughthenfkbslc1a3axis AT taozhang sumospecificpeptidase5promotesoesophagealsquamouscellcarcinomagrowththroughthenfkbslc1a3axis AT renfengwang sumospecificpeptidase5promotesoesophagealsquamouscellcarcinomagrowththroughthenfkbslc1a3axis AT shaoyuanzhang sumospecificpeptidase5promotesoesophagealsquamouscellcarcinomagrowththroughthenfkbslc1a3axis AT lijietan sumospecificpeptidase5promotesoesophagealsquamouscellcarcinomagrowththroughthenfkbslc1a3axis AT guipingyu sumospecificpeptidase5promotesoesophagealsquamouscellcarcinomagrowththroughthenfkbslc1a3axis |