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
ARTICLE HIGHLIGHTS
Research background

Studies of heterogeneous ribonucleoprotein A1 (hnRNPA1) isoforms are rare, and miR-490-3p targeting hnRNPA1-b to regulate colon cancer proliferation has not been reported.

Research motivation

To explore the mechanisms by which miR-490-3p and hnRNPA1-b interact with the PI3K/AKT pathway to regulate the Warburg effect and proliferation of colon cancer cells.

Research objectives

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

Research methods

Paraffin-embedded pathological sections were obtained from 220 colon cancer patients for immunohistochemical analysis to determine the expression of hnRNPA1-b. The study investigated the relationship between the expression values and the clinicopathological features of the patients. 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 assessed using cell counting kit-8 and 5-ethynyl-2’-deoxyuridine assays, and cell cycle and apoptosis were evaluated 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 through glucose uptake and lactic acid production assays.

Research results

The expression of hnRNPA1-b was significantly increased in colon cancer (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.

Research conclusions

These findings suggest that the novel miR-1-3p/hnRNPA1-b/PKM2 axis could provide a new strategy for the diagnosis and treatment of CC.

Research perspectives

The follow-up plan is to study the mechanism of hnRNPA1-b promoting colon cancer metastasis and drug resistance.