Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. May 15, 2024; 16(5): 2038-2059
Published online May 15, 2024. doi: 10.4251/wjgo.v16.i5.2038
Novel miR-490-3p/hnRNPA1-b/PKM2 axis mediates the Warburg effect and proliferation of colon cancer cells via the PI3K/AKT pathway
Xiang-Hui Wan, Guo-Bing Jin, Qun Yang, Ji-Long Hu, Zhi-Liang Liu, Jun Rao, Can Wen, Peng-Ling Li, Xi-Mei Yang, Bo Huang, Xiao-Zhong Wang
Xiang-Hui Wan, Jiangxi Medical College, Nanchang University, Nanchang 330029, Jiangxi Province, China
Xiang-Hui Wan, Guo-Bing Jin, Qun Yang, Can Wen, Peng-Ling Li, Department of Clinical Laboratory, Jiangxi Cancer Hospital, Nanchang 330029, Jiangxi Province, China
Xiang-Hui Wan, Jiangxi Key Laboratory of Translational Research for Cancer, Jiangxi Cancer Hospital, Nanchang 330029, Jiangxi Province, China
Ji-Long Hu, Department of Abdominal Surgery, Jiangxi Cancer Hospital, Nanchang 330029, Jiangxi Province, China
Zhi-Liang Liu, Department of Pathology, Jiangxi Cancer Hospital, Nanchang 330029, Jiangxi Province, China
Jun Rao, Science and Education Section, Jiangxi Cancer Hospital, Nanchang 330029, Jiangxi Province, China
Xi-Mei Yang, Department of Clinical Laboratory, Jiangxi Children’s Hospital, Nanchang 330006, Jiangxi Province, China
Bo Huang, Xiao-Zhong Wang, Department of Clinical Laboratory, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
Xiao-Zhong Wang, Jiangxi Province Key Laboratory of Laboratory Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
Author contributions: Wan XH and Wang XZ participated in study design and drafted the manuscript; Jin GB and Yang Q performed the data curation and analysis; Hu JL, Liu ZL, Rao J, Wen C, and Li PL carried out the experiments and prepared the figures; Yang XM and Huang B supervised the research; and all authors have read and approved the final manuscript.
Supported by the National Natural Science Foundation of China, No. 82160405; Jiangxi Provincial Natural Science Foundation, No. 20232BAB206131, No. 20212ACB206016, and No. 20224BAB206114; Jiangxi Provincial Health Commission Project, No. 202310887; and the Development Fund of Jiangxi Cancer Hospital, No. 2021J10.
Institutional review board statement: The study was reviewed and approved by the Ethics Committee of Jiangxi Cancer Hospital, No. 2023ky089.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The data sets used and analyzed during the current study are available from the corresponding author on reasonable request.
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: Xiao-Zhong Wang, PhD, Doctor, Department of Clinical Laboratory, The Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Nanchang 330006, Jiangxi Province, China. wangxiaozhong@ncu.edu.cn
Received: November 20, 2023
Peer-review started: November 20, 2023
First decision: December 29, 2023
Revised: January 9, 2024
Accepted: March 11, 2024
Article in press: March 11, 2024
Published online: May 15, 2024
Processing time: 170 Days and 22.8 Hours
Abstract
BACKGROUND

Heterogeneous ribonucleoprotein A1 (hnRNPA1) has been reported to enhance the Warburg effect and promote colon cancer (CC) cell proliferation, but the role and mechanism of the miR-490-3p/hnRNPA1-b/PKM2 axis in CC have not yet been elucidated.

AIM

To investigate the role and mechanism of a novel miR-490-3p/hnRNPA1-b/PKM2 axis in enhancing the Warburg effect and promoting CC cell proliferation through the PI3K/AKT pathway.

METHODS

Paraffin-embedded pathological sections from 220 CC patients were collected and subjected to immunohistochemical analysis to determine the expression of hnRNPA1-b. The relationship between the expression values and the clinicopathological features of the patients was investigated. Differences in mRNA expression were analyzed using quantitative real-time polymerase chain reaction, while differences in protein expression were analyzed using western blot. Cell proliferation was evaluated using the cell counting kit-8 and 5-ethynyl-2’-deoxyuridine assays, and cell cycle and apoptosis were detected using flow cytometric assays. The targeted binding of miR-490-3p to hnRNPA1-b was validated using a dual luciferase reporter assay. The Warburg effect was evaluated by glucose uptake and lactic acid production assays.

RESULTS

The expression of hnRNPA1-b was significantly increased in CC tissues and cells compared to normal controls (P < 0.05). Immunohistochemical results demonstrated significant variations in the expression of the hnRNPA1-b antigen in different stages of CC, including stage I, II-III, and IV. Furthermore, the clinicopathologic characterization revealed a significant correlation between hnRNPA1-b expression and clinical stage as well as T classification. HnRNPA1-b was found to enhance the Warburg effect through the PI3K/AKT pathway, thereby promoting proliferation of HCT116 and SW620 cells. However, the proliferation of HCT116 and SW620 cells was inhibited when miR-490-3p targeted and bound to hnRNPA1-b, effectively blocking the Warburg effect.

CONCLUSION

These findings suggest that the novel miR-490-3p/hnRNPA1-b/PKM2 axis could provide a new strategy for the diagnosis and treatment of CC.

Keywords: Heterogeneous ribonucleoprotein A1-b; MiR-490-3p; Colon cancer; Alternative splicing; Warburg effect

Core Tip: Currently, there are no ideal early diagnostic markers or specific target drugs available for the treatment of colon cancer (CC). This study confirmed the role of heterogeneous ribonucleoprotein A1 (hnRNPA1)’s selective shear monomer, hnRNPA1-b, in promoting the proliferation of CC cells and elucidated the mechanism of action of the miR-490-3p/hnRNPA1-b/PKM2 axis in modulating the proliferation of CC cells by remodeling the Warburg effect through the PI3K/AKT pathway. These findings could provide a new strategy for the diagnosis and treatment of CC.