Clinical and Translational Research
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. May 15, 2024; 16(5): 1890-1907
Published online May 15, 2024. doi: 10.4251/wjgo.v16.i5.1890
SERPINH1 promoted the proliferation and metastasis of colorectal cancer by activating PI3K/Akt/mTOR signaling pathway
Xiao-Sheng Jin, Lu-Xi Chen, Ting-Ting Ji, Rong-Zhou Li
Xiao-Sheng Jin, Lu-Xi Chen, Ting-Ting Ji, Rong-Zhou Li, Department of Gastroenterology, The Third Affiliated Hospital of Wenzhou Medical University, Ruian 325000, Zhejiang Province, China
Author contributions: Jin XS, Chen LX, Ji TT, and Li RZ designed the research; Jin XS performed the research and wrote the paper; Li RZ supervised the report; Chen LX contributed to the analysis; Ji TT provided constructive advice; and all the authors read and approved the final manuscript.
Supported by Ruian Natural Science Foundation, No. MS2021008.
Institutional review board statement: This study was approved by the Ethics Committee of the Third Affiliated Hospital of Wenzhou Medical University, No. YJ2022043.
Clinical trial registration statement: This study did not involve any clinical trials.
Informed consent statement: The specimens involved in this study have been obtained with signed informed consent from the patients.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The original contributions presented in the study are included in the article materials. Further inquiries can be directed to the corresponding authors.
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: Rong-Zhou Li, MD, Professor, Department of Gastroenterology, The Third Affiliated Hospital of Wenzhou Medical University, No. 108 Wansong Road, Ruian 325000, Zhejiang Province, China. lrz23228@163.com
Received: October 19, 2023
Peer-review started: October 19, 2023
First decision: December 29, 2023
Revised: January 10, 2024
Accepted: March 14, 2024
Article in press: March 14, 2024
Published online: May 15, 2024
Processing time: 202 Days and 21.5 Hours
Abstract
BACKGROUND

Serpin peptidase inhibitor clade H member 1 (SERPINH1) was initially recognized as an oncogene implicated in various human malignancies. Nevertheless, the clinical relevance and functional implications of SERPINH1 in colorectal cancer (CRC) remain largely elusive.

AIM

To investigate the effects of SERPINH1 on CRC cells and its specific mechanism.

METHODS

Quantitative real-time polymerase chain reaction, western blotting analysis, The Cancer Genome Atlas data mining and immunohistochemistry were employed to examine SERPINH1 expression in CRC cell lines and tissues. A series of in-vitro assays were performed to demonstrate the function of SERPINH1 and its possible mechanisms in CRC.

RESULTS

SERPINH1 demonstrated elevated expression levels in both CRC cells and tissues, manifested at both mRNA and protein tiers. Elevated SERPINH1 levels correlated closely with advanced T stage, lymph node involvement, and distant metastasis, exhibiting a significant association with poorer overall survival among CRC patients. Subsequent investigations unveiled that SERPINH1 overexpression notably bolstered CRC cell proliferation, invasion, and migration in vitro, while conversely, SERPINH1 knockdown elicited the opposite effects. Gene set enrichment analysis underscored a correlation between SERPINH1 upregulation and genes associated with cell cycle regulation. Our findings underscored the capacity of heightened SERPINH1 levels to expedite G1/S phase cell cycle progression via phosphatidylinositol 3-kinase/AKT/mechanistic target of rapamycin pathway activation, thereby facilitating CRC cell invasion and migration.

CONCLUSION

These findings imply a crucial involvement of SERPINH1 in the advancement and escalation of CRC, potentially positioning it as a novel candidate for prognostic assessment and therapeutic intervention in CRC management.

Keywords: Serpin peptidase inhibitor clade H member 1, Colorectal cancer, Proliferation, Cell cycle, Phosphatidylinositol 3-kinase/AKT/mechanistic target of rapamycin

Core Tip: The expression of serpin peptidase inhibitor clade H member 1 (SERPINH1) was observed to be elevated in both colorectal cancer (CRC) cells and tissues at mRNA and protein levels. Increased SERPINH1 expression demonstrated a close association with the T stage, lymph node status, and distant metastasis in CRC patients, displaying a significant correlation with poor overall survival. Subsequent investigations revealed that the overexpression of SERPINH1 markedly enhanced the in vitro proliferation, invasion, and migration capabilities of CRC cells. Conversely, the knockdown of SERPINH1 resulted in the opposite effects. In addition, our study validated that the overexpression of SERPINH1 could stimulate the G1/S phase cell cycle transition through the activation of the phosphatidylinositol 3-kinase (PI3K)/AKT/mechanistic target of rapamycin (mTOR) pathways. Additionally, it was observed that the overexpression of SERPINH1 facilitated cell invasion and migration by modulating the PI3K/AKT/mTOR pathway. These findings emphasize the pivotal role of SERPINH1 in promoting CRC progression, providing insights into its potential as a therapeutic target for CRC treatment.