Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Jul 15, 2024; 16(7): 3241-3255
Published online Jul 15, 2024. doi: 10.4251/wjgo.v16.i7.3241
RBM5 suppresses proliferation, metastasis and glycolysis of colorectal cancer cells via stabilizing phosphatase and tensin homolog mRNA
Chu-Xiang Wang, Feng Liu, Yi Wang
Chu-Xiang Wang, Department of Anorectal Surgery, The Affiliated Hospital of Dalian Medical University, Dalian 116000, Liaoning Province, China
Feng Liu, Department of Scientific Research, Beijing Fresta Technologies Co, Ltd., Beijing 100176, China
Yi Wang, Department of VIP Medical Services, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
Author contributions: Wang CX and Wang Y designed the study; Wang CX, Liu F, and Wang Y carried out experiments; Liu F and Wang Y analyzed experimental results; Wang CX was a major contributor in writing the manuscript; and all authors reviewed and approved the manuscript.
Institutional animal care and use committee statement: Animal experiments were executed in accordance with the Animal Care and Use Committee of Beijing Viewsolid Biotechnology Co. LTD (Approval No. VS2126A00176).
Conflict-of-interest statement: All authors have nothing to disclose.
Data sharing statement: The authors confirm that the data supporting the findings of this study are available within the article.
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: Yi Wang, MD, Associate Chief Physician, Department of VIP Medical Services, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17 Panjiayuan Nanli, Chaoyang District, Beijing 100021, China. dr_wangyi1018@163.com
Received: February 29, 2024
Revised: May 7, 2024
Accepted: May 24, 2024
Published online: July 15, 2024
Processing time: 134 Days and 13.3 Hours
Abstract
BACKGROUND

RNA binding motif 5 (RBM5) has emerged as crucial regulators in many cancers.

AIM

To explore more functional and mechanistic exploration of RBM5 since the lack of research on RBM5 in colorectal cancer (CRC) dictates that is essential.

METHODS

Through Gene Expression Profiling Interactive Analysis, we analyzed RBM5 expression in colon adenocarcinoma and rectum adenocarcinoma tissues. For detecting the mRNA expression of RBM5, quantitative real time-polymerase chain reaction was performed. Protein expression levels of RBM5, hexokinase 2, lactate dehydrogenase A, phosphatase and tensin homolog (PTEN), phosphoinositide 3-kinase (PI3K), phosphorylated-protein kinase B (p-AKT), and AKT were determined via Western blot. Functionally, cell counting kit-8 and 5-ethynyl-2’-deoxyuridine (EDU) assay were performed to evaluate proliferation of CRC cells. Invasiveness and migration of CRC cells were evaluated through conducting transwell assays. Glucose consumption, lactate production and adenosine-triphosphate (ATP) production were measured through a glucose assay kit, a lactate assay kit and an ATP production assay kit, respectively. Besides, RNA immunoprecipitation assay, half-life RT-PCR and dual-luciferase reporter assay were applied to detect interaction between RBM5 and PTEN. To establish a xenotypic tumor mice, CRC cells were subcutaneously injected into the right flank of each mouse. Protein expression of RBM5, Ki67, and PTEN in tumor tissues was examined using immunohistochemistry staining. Haematoxylin and eosin staining was used to evaluate tumor liver metastasis in mice.

RESULTS

We discovered down-regulation of RBM5 expression in CRC tissues and cells. RBM5 overexpression repressed proliferation, migration and invasion of CRC cells. Meantime, RBM5 impaired glycolysis in CRC cells, presenting as decreased glucose consumption, decreased lactate production and decreased ATP production. Besides, RBM5 bound to PTEN mRNA to stabilize its expression. PTEN expression was positively regulated by RBM5 in CRC cells. The protein levels of PI3K and p-AKT were significantly decreased after RBM5 overexpression. The suppressive influences of RBM5 on glycolysis, proliferation and metastasis of CRC cells were partially counteracted by PTEN knockdown. RBM5 suppressed tumor growth and liver metastasis in vivo.

CONCLUSION

This investigation provided new evidence that RBM5 was involved in CRC by binding to PTEN, expanding the importance of RBM5 in the treatment of CRC.

Keywords: Colorectal cancer, RNA binding motif 5, Phosphatase and tensin homolo, Phosphoinositide 3-kinase/anti-protein kinase, Glycolysis

Core Tip: RNA binding motif 5 (RBM5) exhibited low expression in colorectal cancer (CRC) tissues and cells. RBM5 retarded tumorigenesis and metastasis of CRC in vitro and in vivo. In terms of mechanism, RBM5 overexpression-induced tumor inhibition of CRC was partially mediated by the phosphatase and tensin homolog/phosphoinositide 3-kinase/anti-protein kinase pathway. These findings extend our knowledge of the link between RBM5 and CRC, shedding light on the mechanisms how RBM5 impair CRC tumorigenesis.