Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Dec 15, 2023; 15(12): 2120-2137
Published online Dec 15, 2023. doi: 10.4251/wjgo.v15.i12.2120
Hsa_circ_0136666 mediates the antitumor effect of curcumin in colorectal carcinoma by regulating CXCL1 via miR-1301-3p
Shi Chen, Wei Li, Chen-Gong Ning, Feng Wang, Li-Xing Wang, Chen Liao, Feng Sun
Shi Chen, Chen-Gong Ning, Feng Wang, Li-Xing Wang, Chen Liao, Feng Sun, Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Kunming Medical University, Kunming 650101, Yunnan Province, China
Wei Li, Department of Blood Transfusion, The Second Affiliated Hospital of Kunming Medical University, Kunming 650101, Yunnan Province, China
Co-first authors: Shi Chen and Wei Li.
Author contributions: Chen S and Li W contributed equally to this work and are co-first authors, including design of the study, acquiring and analyzing data from experiments, and writing of the actual manuscript. Chen S, Li W, Li W and Wang F conceived and designed the experiments; Liao C, Chen S, Wang F and Ning CG performed the research; Ning CG, Wang LX, and Sun F contributed to the statistical analysis; Chen S, Li W, Wang F and Ning CG wrote the paper; including design of the study, acquiring and analyzing data from experiments, and writing of the actual manuscript. All authors read and approved the final manuscript.
Supported by National Natural Science Foundation of China, No. 81960508; Yunnan Province Wang Bin Expert Workstation, No. 202205AF150011.
Institutional review board statement: This study did not involve any human studies.
Institutional animal care and use committee statement: The experimental protocol was approved by the Animal Care and Use Committee of The Second Affiliated Hospital of Kunming Medical University.
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: Feng Sun, PhD, Doctor, Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Kunming Medical University, No. 374 Yunnan-Myanmar Avenue, Wuhua District, Kunming 650101, Yunnan Province, China. sunfeng1971@163.com
Received: July 27, 2023
Peer-review started: July 27, 2023
First decision: August 8, 2023
Revised: September 22, 2023
Accepted: October 16, 2023
Article in press: October 16, 2023
Published online: December 15, 2023
Processing time: 140 Days and 1.9 Hours
ARTICLE HIGHLIGHTS
Research background

Colorectal carcinoma (CRC) is the most frequent-occurring malignant tumour in the United States. Curcumin exerts anti-tumor activity in CRC, but the underlying mechanism needs further elucidation. Meanwhile, over the last decade, circular RNAs (circRNAs) is correlated with the initiation and development of various tumors, containing CRC. Also, the increasing focus on the competing endogenous RNAs hypothesis is that circRNAs serve as microRNA sponges to derepress target mRNAs’ levels.

Research motivation

Clinically, it is urgent to find a more effective therapy, which has high clinical significance for CRC patients. Currently, the chemo-preventive properties of traditional Chinese medicine have drawn great attention in cancer therapeutics. As a naturally occurring medicine, curcumin is derived from the medical plant Curcuma longa L. However, it needs further investigation regarding the mechanism through which curcumin affects CRC development.

Research objectives

This study aims at illuminating whether hsa_circ_0136666 involvement on curcumin-triggered CRC progression was mediated via sponging miR-1301-3p.

Research methods

CRC cells were adopted and treated with 20 μM curcumin for 24 h. Then, for hsa_circ_0136666 stably upregulation, CRC cells were treated with hsa_circ_0136666 overexpression vector transfection or miR-1301-3p mimic and inhibitor. Real-time quantitative PCR was used to quantified the expression of hsa_circ_0136666, miR-1301-3p and CXCL1. Cell counting kit-8, colony-forming cell, 5-ethynyl-2’-deoxyuridine, and flow cytometry assays were carried out to determine cell proliferation, apoptosis, and cell cycle progression. The relationship between hsa_circ_0136666, miR-1301-3p and CXCL1 were validated by RNA pull-down, RIP, and dual-luciferase reporter assay. In vivo experiments were implemented by the murine xenograft model.

Research results

Curcumin treatment could distinctly reduce the colony number of SW480 and SW620 cells relative to their control groups. Furthermore, the apoptosis rate in the curcumin group was markedly improved in comparison with other groups Interestingly, curcumin treatment significantly decreased hsa_circ_0136666 in SW480 and SW620 but had no effect on hsa_circ_0000392 and hsa_circ_0000896 expression. These data indicated the suppressive role of curcumin on CRC development. hsa_circ_0136666 upregulation could abolish the impacts of curcumin on CRC cell growth and apoptosis. Meanwhile, miR-1301-3p acted as a direct target of hsa_circ_0136666 and miR-1301-3p directly targeted CXCL1. Hsa_circ_0136666 could reverse curcumin-triggered CRC cell proliferation and apoptosis by interacting with miR-1301-3p while miR-1301-3p knockdown overturned curcumin-induced increase in CRC cell growth and decrease in apoptosis by targeting CXCL1. Curcumin repressed CRC cell growth via regulating hsa_circ_0136666 in vivo.

Research conclusions

Curcumin repressed CRC cell proliferation and boosted apoptosis, and first verified it was associated with the regulatory network of the hsa_circ_0136666/miR-1301-3p/CXCL1. Hsa_circ_0136666 relieves curcumin-induced CRC cell growth and apoptosis partly via the miR-1301-3p/CXCL1 signaling.

Research perspectives

This study elucidates a new mechanism of curcumin and sheds light on developing a new therapeutic for CRC treatment.