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Updated: Aug 9, 2025
Detection of Alternative Splicing During Epithelial-Mesenchymal Transition
Published on: October 9, 2014
CD44 occurring alternative splicing promotes cisplatin resistance and evokes tumor immune response in oral squamous
Xue Qiao1, Li Zhu2, Rongbo Song2
1Department of Central Laboratory, School and Hospital of Stomatology, Liaoning Provincial Key Laboratory of Oral Disease, China Medical University, Shenyang, Liaoning 110002, China; Department of Oral Biology, School and Hospital of Stomatology, Liaoning Provincial Key Laboratory of Oral Disease, China Medical University, Shenyang, Liaoning, China.
Background:
Oral squamous cell carcinoma (OSCC) is the most prevalent malignant tumor in head and neck region. Platinum drug resistance limits the clinical application of chemotherapy regardless of medical development. The aim of our study is to identify cisplatin-resistant genes which can be used as new therapeutic targets and investigate the functional mechanism of OSCC chemoresistance.
Methods:
The OSCC Cal27 and HSC4 cisplatin-resistant cell lines were constructed to screen the differential genes/transcripts expression. GO, KEGG and GSEA were performed to reveal the relevant signaling pathways. Alternative splicing (AS) software rMATs was applied to explore AS events in chemoresistance. R package and TIMER tools were used to evaluate the linear correlation between CD44 and immune cell subpopulations. The co-culture model of dendritic cells (DCs) and OSCC cells was applied to explore the effect of CD44 on immune microenvironment and cisplatin resistance.
Results:
Our results showed that CD44 was differentially expressed in cisplatin-resistant OSCC cells. Through bioinformatics prediction and experimental verification, we confirmed that CD44 occurring AS was involved in tumor progression and cisplatin resistance. Moreover, CD44 could further enhance the cisplatin resistance of OSCC by activating DCs, making CD44 to be a potential intervention target. We also identified DC as a new target for platinum drugs to stimulate the growth of OSCC.
Conclusion:
Our findings not only make it possible to explore new therapeutic methods, such as CD44 inhibitors or antisense oligonucleotides, but also provide insights into the new mechanisms of cisplatin resistance to chemotherapy.
Insights
CD44 alternative splicing (AS) promotes cisplatin resistance in oral squamous cell carcinoma (OSCC) by activating dendritic cells (DCs). Targeting CD44 offers new therapeutic strategies for overcoming chemotherapy resistance in OSCC.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Oral squamous cell carcinoma (OSCC) is a common head and neck cancer.
- Platinum drug resistance remains a significant challenge in OSCC chemotherapy.
- Identifying novel therapeutic targets is crucial for improving treatment outcomes.
Purpose of the Study:
- To identify genes associated with cisplatin resistance in OSCC.
- To investigate the functional mechanisms underlying OSCC chemoresistance.
- To explore CD44 as a potential therapeutic target.
Main Methods:
- Construction of cisplatin-resistant OSCC cell lines (Cal27, HSC4).
- Differential gene/transcript expression screening.
- Bioinformatic analyses (GO, KEGG, GSEA) and alternative splicing analysis (rMATS).
- Correlation analysis of CD44 with immune cells (R package, TIMER).
- Co-culture model of dendritic cells (DCs) and OSCC cells.
Main Results:
- CD44 exhibited differential expression in cisplatin-resistant OSCC cells.
- CD44 alternative splicing (AS) was confirmed to be involved in OSCC progression and cisplatin resistance.
- CD44 enhances cisplatin resistance by activating DCs, suggesting CD44 as an intervention target.
- DCs were identified as a novel target for platinum drugs in OSCC growth stimulation.
Conclusions:
- CD44 inhibitors or antisense oligonucleotides represent potential therapeutic strategies.
- The study provides new insights into the mechanisms of cisplatin resistance in OSCC.
- Targeting CD44 and its interaction with the immune microenvironment may overcome chemotherapy resistance.
