Published online Apr 15, 2024. doi: 10.4251/wjgo.v16.i4.1564
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
Processing time: 111 Days and 0.8 Hours
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.
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.
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.
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.
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.
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.
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.