Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 14, 2024; 30(26): 3229-3246
Published online Jul 14, 2024. doi: 10.3748/wjg.v30.i26.3229
Loss of monopolar spindle-binding protein 3B expression promotes colorectal cancer invasiveness by activation of target of rapamycin kinase/autophagy signaling
Juan Sun, Jin-Xiu Zhang, Meng-Shi Li, Meng-Bin Qin, Ruo-Xi Cheng, Qing-Ru Wu, Qiu-Ling Chen, Dan Yang, Cun Liao, Shi-Quan Liu, Jie-An Huang
Juan Sun, Jin-Xiu Zhang, Meng-Shi Li, Meng-Bin Qin, Ruo-Xi Cheng, Qing-Ru Wu, Qiu-Ling Chen, Dan Yang, Shi-Quan Liu, Jie-An Huang, Department of Gastroenterology, The Second Affiliated Hospital of Guangxi Medical University, Nanning 530007, Guangxi Zhuang Autonomous Region, China
Cun Liao, Department of Colorectal & Anal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Co-first authors: Juan Sun and Jin-Xiu Zhang.
Author contributions: Sun J and Zhang JX contributed equally to this study; Sun J, Zhang JX, and Huang JA developed the original hypothesis, supervised the experimental design, and wrote and revised the manuscript; Sun J, Zhang JX, Li MS, and Qin MB performed in vitro and in vivo experiments; Qin MB, Cheng RX, Wu QR, and Liao C participated in the clinical specimens collection; Sun J, Zhang JX, Chen QL, Yang D, and Liu SQ analyzed the data and performed statistical analysis; and all authors read and approved the final manuscript.
Supported by National Natural Science Foundation of China, No. 81760516; Natural Science Foundation of Guangxi, China, No. 2019GXNSFAA185030; Self-Financed Scientific Research Projects of Guangxi Zhuang Autonomous Region Health and Family Planning Commission, China, No. Z20181003; and Guangxi Medical University Youth Science Fund Project, China, No. GXMUYSF202221.
Institutional review board statement: The study was reviewed and approved by the First Affiliated Hospital of Guangxi Medical University Institutional Review Board (Approval No. 2022-E335-01).
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Guangxi Medical University (Protocol No. 202108006).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
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: Jie-An Huang, PhD, Chief Physician, Professor, Department of Gastroenterology, The Second Affiliated Hospital of Guangxi Medical University, No. 166 Daxue East Road, Xixiangtang District, Nanning 530007, Guangxi Zhuang Autonomous Region, China. hjagxmu@163.com
Received: April 30, 2024
Revised: May 28, 2024
Accepted: June 3, 2024
Published online: July 14, 2024
Processing time: 69 Days and 19.4 Hours
Abstract
BACKGROUND

Monopolar spindle-binding protein 3B (MOB3B) functions as a signal transducer and altered MOB3B expression is associated with the development of human cancers.

AIM

To investigate the role of MOB3B in colorectal cancer (CRC).

METHODS

This study collected 102 CRC tissue samples for immunohistochemical detection of MOB3B expression for association with CRC prognosis. After overexpression and knockdown of MOB3B expression were induced in CRC cell lines, changes in cell viability, migration, invasion, and gene expression were assayed. Tumor cell autophagy was detected using transmission electron microscopy, while nude mouse xenograft experiments were performed to confirm the in-vitro results.

RESULTS

MOB3B expression was reduced in CRC vs normal tissues and loss of MOB3B expression was associated with poor CRC prognosis. Overexpression of MOB3B protein in vitro attenuated the cell viability as well as the migration and invasion capacities of CRC cells, whereas knockdown of MOB3B expression had the opposite effects in CRC cells. At the molecular level, microtubule-associated protein light chain 3 II/I expression was elevated, whereas the expression of matrix metalloproteinase (MMP)2, MMP9, sequestosome 1, and phosphorylated mechanistic target of rapamycin kinase (mTOR) was downregulated in MOB3B-overexpressing RKO cells. In contrast, the opposite results were observed in tumor cells with MOB3B knockdown. The nude mouse data confirmed these in-vitro findings, i.e., MOB3B expression suppressed CRC cell xenograft growth, whereas knockdown of MOB3B expression promoted the growth of CRC cell xenografts.

CONCLUSION

Loss of MOB3B expression promotes CRC development and malignant behaviors, suggesting a potential tumor suppressive role of MOB3B in CRC by inhibition of mTOR/autophagy signaling.

Keywords: Colorectal cancer; Monopolar spindle-binding protein 3B; Mechanistic target of rapamycin kinase; Autophagy; Prognosis

Core Tip: Monopolar spindle-binding protein 3B (MOB3B) functions as a signal transducer and altered MOB3B expression is associated with the development of human cancers. In this study, we investigated the effects of MOB3B in colorectal cancer (CRC). We found that loss of MOB3B expression promoted CRC development and malignant behaviors, suggesting a potential tumor suppressive role of MOB3B in CRC by inhibition of mechanistic target of rapamycin kinase/autophagy signaling.