Meng ZS, Hu JT, Wu H, Li BK. Inhibition of the SERPINB5/HSP90AA1 axis restrains the proliferation and invasion of rectal cancer. World J Gastroenterol 2025; 31(11): 103412 [PMID: 40124262 DOI: 10.3748/wjg.v31.i11.103412]
Corresponding Author of This Article
Bao-Kun Li, MD, Second Departments Surgery, The Fourth Hospital of Hebei Medical University, No. 12 Jiankang Road, Shijiazhuang 050011, Hebei Province, China. libaokun@hebmu.edu.cn
Research Domain of This Article
Oncology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastroenterol. Mar 21, 2025; 31(11): 103412 Published online Mar 21, 2025. doi: 10.3748/wjg.v31.i11.103412
Inhibition of the SERPINB5/HSP90AA1 axis restrains the proliferation and invasion of rectal cancer
Ze-Song Meng, Ji-Tao Hu, Hao Wu, Bao-Kun Li
Ze-Song Meng, Ji-Tao Hu, Bao-Kun Li, Second Departments Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei Province, China
Hao Wu, Clinical Laboratory of East Hospital, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei Province, China
Author contributions: Meng ZS and Li BK designed the experiments and conducted clinical data collection; Hu JT and Wu H performed postoperative follow-up and recorded the data; Meng ZS and Li BK conducted the collation and statistical analysis, and wrote the original manuscript and revised the paper; and all authors read and approved the final manuscript.
Supported by the Medical Science Research Project Plan of the Hebei Provincial Health Commission, No. 20210027.
Institutional review board statement: This study was approved by the Medical Ethics Committee of the Fourth Hospital of Hebei Medical University.
Institutional animal care and use committee statement: Institutional animal care and use committee statement: All animal experiments were approved by the Ethics Committee of the Fourth Hospital of Hebei Medical University (No. 20250158).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: All data generated or analyzed during this study are included in this published article.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Bao-Kun Li, MD, Second Departments Surgery, The Fourth Hospital of Hebei Medical University, No. 12 Jiankang Road, Shijiazhuang 050011, Hebei Province, China. libaokun@hebmu.edu.cn
Received: November 26, 2024 Revised: January 10, 2025 Accepted: February 8, 2025 Published online: March 21, 2025 Processing time: 107 Days and 4.5 Hours
Abstract
BACKGROUND
The upregulation of serpin family B member 5 (SERPINB5) has been linked to the progression of rectal cancer. However, the specific roles and underlying mechanisms of SERPINB5 in rectal cancer are not fully understood.
AIM
To investigate the roles and mechanisms of SERPINB5 in rectal cancer.
METHODS
SERPINB5 protein level in rectal cancer tissues and cell lines was measured through western blot analysis. SW480 cells were transfected with pcDNA-SERPINB5 or short-hairpin RNA targeting SERPINB5 (sh-SERPINB5). Cell proliferation, invasion, and apoptosis were then evaluated. The interaction between SERPINB5 and heat shock protein 90 alpha class A member 1 (HSP90AA1) was confirmed through a co-immunoprecipitation assay. Subsequently, pcDNA-HSP90AA1 or sh-HSP90AA1 was transfected into SW480 cells, and cell progression was then detected. Moreover, rescue experiments were used to investigate the effect of the SERPINB5/HSP90AA1 axis on rectal cancer progression. Additionally, sh-SERPINB5-transfected SW480 cells were implanted into nude mice, and xenograft tumor growth was then evaluated.
RESULTS
SERPINB5 was prominently upregulated in rectal cancer tissues and cells. SERPINB5 overexpression increased SW480 cell proliferation and invasion while reducing apoptosis. In contrast, SERPINB5 knockdown had the opposite effects. Moreover, SERPINB5 could interact with HSP90AA1 and promote HSP90AA1 expression in SW480 cells. HSP90AA1 overexpression facilitated SW480 cell proliferation and invasion and restrained apoptosis. By contrast, HSP90AA1 knockdown suppressed cell progression. The upregulation of HSP90AA1 reversed the SERPINB5 silencing-mediated inhibition of SW480 cell progression. Additionally, SERPINB5 knockdown retarded the growth of rectal cancer tumors in vivo.
CONCLUSION
SERPINB5 knockdown inhibited rectal cancer cell proliferation and invasion and retarded xenograft tumor growth by inhibiting HSP90AA1 expression.
Core Tip: This study suggested that serpin family B member 5 (SERPINB5) was significantly upregulated in rectal cancer tissues and cell lines. SERPINB5 overexpression increased SW480 cell proliferation and invasion while reducing apoptosis. By contrast, SERPINB5 knockdown had the opposite effects. Moreover, SERPINB5 knockdown retarded the growth of rectal cancer tumors in vivo. Mechanistically, SERPINB5 interacted with heat shock protein 90 alpha family class A member 1 and promoted heat shock protein 90 alpha family class A member 1 expression in SW480 cells.
