Basic Study
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Apr 15, 2024; 16(4): 1564-1577
Published online Apr 15, 2024. doi: 10.4251/wjgo.v16.i4.1564
Upregulated lncRNA PRNT promotes progression and oxaliplatin resistance of colorectal cancer cells by regulating HIPK2 transcription
Sai-Nan Li, Shan Yang, Hao-Qi Wang, Tian-Li Hui, Meng Cheng, Xi Zhang, Bao-Kun Li, Gui-Ying Wang
Sai-Nan Li, Shan Yang, Hao-Qi Wang, Tian-Li Hui, Meng Cheng, Xi Zhang, The First Department of Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei Province, China
Sai-Nan Li, Bao-Kun Li, Gui-Ying Wang, The Second Department of Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei Province, China
Gui-Ying Wang, Department of General Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China
Author contributions: Li SN and Wang GY contributed to conception, design and writing of the manuscript; Li SN, Hui TL, Yang S, Zhang X and Wang HQ performed the research; Cheng M, Li BK and Li SN contributed to analysis and interpretation of data; and all authors read and approved the final manuscript.
Supported by Hebei Provincial Health Commission Youth Science and Technology Project, No. 20210027.
Institutional review board statement: The study was reviewed and approved by the Fourth Yuan Medical Ethics Committee of Hebei Medical University, No. 2023KS025.
Institutional animal care and use committee statement: All experiments with designed animals were reviewed and approved by the Ethics Committee for Laboratory Animal Welfare of the Fourth Hospital of Hebei Medical University, No. IACUC-4th Hos Hebmu-.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: All data are available from the corresponding author.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines and have prepared and revised the manuscript 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: Gui-Ying Wang, PhD, Surgeon, Department of General Surgery, The Second Hospital of Hebei Medical University, No. 215 Heping West Road, Shijiazhuang 050000, Hebei Province, China. hebeiwangguiying@163.com
Received: December 22, 2023
Peer-review started: December 22, 2023
First decision: January 9, 2024
Revised: January 26, 2024
Accepted: February 18, 2024
Article in press: February 18, 2024
Published online: April 15, 2024
ARTICLE HIGHLIGHTS
Research background

Colorectal cancer ranks as the third most prevalent form of cancer and is the second leading cause of cancer-related mortality worldwide. The development of chemotherapy resistance, especially to the drug oxaliplatin, remains a significant hurdle in the treatment of colorectal cancer, leading to reduced efficacy of anticancer drugs and worsening patient outcomes.

Research motivation

This study is driven by the recognition that long noncoding RNAs (lncRNAs) play a crucial role in the pathophysiology of cancer, including the development of chemotherapy resistance. However, the specific lncRNAs contributing to resistance in colorectal cancer treatment, particularly involving oxaliplatin, are not fully identified or understood.

Research objectives

The primary aim of this research is to delve into the role of lncRNAs in the resistance against oxaliplatin in colorectal cancer cells and to specifically pinpoint and characterize the function of the lncRNA prion protein testis specific (PRNT) in the modulation of this resistance and the overall progression of colorectal cancer.

Research methods

The study approaches its objectives through the analysis of datasets from the Gene Expression Omnibus database, identifying potential lncRNAs and mRNAs that are involved in oxaliplatin resistance. A series of methodologies, including quantitative real-time polymerase chain reaction, MTT assays, wound healing, and Transwell assays, in addition to Western blotting and xenograft mouse modeling, were employed to investigate the interactions and effects within the PRNT/zinc finger protein 184 (ZNF184)/homeodomain interacting protein kinase 2 (HIPK2) regulatory axis.

Research results

It was found that the expression of lncRNA PRNT is higher in oxaliplatin-resistant colorectal cancer cell lines. PRNT appears to function by sponging the transcription factor ZNF184, which in turn regulates the expression of HIPK2, a gene inversely correlated with oxaliplatin resistance. The manipulation of PRNT levels was shown to alter the sensitivity of colorectal cancer cells to oxaliplatin, both in laboratory and animal models.

Research conclusions

The study concludes that PRNT significantly contributes to the progression of colorectal cancer and to the resistance against oxaliplatin by interacting with ZNF184 and regulating HIPK2 expression. These findings illuminate a novel pathway of chemotherapy resistance in colorectal cancer and suggest that PRNT could be a promising target for therapeutic intervention in CRC patients undergoing oxaliplatin-based chemotherapy.

Research perspectives

Looking ahead, the research suggests that future work should explore the potential for clinical application of PRNT-targeted therapies in colorectal cancer. There is also a need for further research to fully understand the impact of the PRNT/ZNF184/HIPK2 axis on colorectal cancer and potentially other cancers, which may open new avenues for overcoming chemotherapy resistance.