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Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
Published on: April 22, 2019
MiR-23a sensitizes nasopharyngeal carcinoma to irradiation by targeting IL-8/Stat3 pathway
Jia-Quan Qu1,2, Hong-Mei Yi1,2, Xu Ye1,2
1Research Center of Carcinogenesis and Targeted Therapy, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Abstract:
Radioresistance poses a major challenge in nasopharyngeal carcinoma (NPC) treatment, but little is known about how miRNA regulates this phenomenon. In this study, we investigated the function and mechanism of miR-23a in NPC radioresistance, one of downregulated miRNAs in the radioresistant NPC cells identified by our previous microarray analysis. We observed that miR-23a was frequently downregulated in the radioresistant NPC tissues, and its decrement correlated with NPC radioresistance and poor patient survival, and was an independent predictor for reduced patient survival. In vitro radioresponse assays showed that restoration of miR-23a expression markedly increased NPC cell radiosensitivity. In a mouse model, therapeutic administration of miR-23a agomir dramatically sensitized NPC xenografts to irradiation. Mechanistically, we found that reduced miR-23a promoted NPC cell radioresistance by activating IL-8/Stat3 signaling. Moreover, the levels of IL-8 and phospho-Stat3 were increased in the radioresistance NPC tissues, and negatively associated with miR-23a level. Our data demonstrate that miR-23a is a critical determinant of NPC radioresponse and prognostic predictor for NPC patients, and its decrement enhances NPC radioresistance through activating IL-8/Stat3 signaling, highlighting the therapeutic potential of miR-23a/IL-8/Stat3 signaling axis in NPC radiosensitization.
Insights
MicroRNA-23a (miR-23a) downregulation promotes radioresistance in nasopharyngeal carcinoma (NPC) by activating IL-8/Stat3 signaling. Restoring miR-23a enhances radiosensitivity and improves patient survival, offering a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Nasopharyngeal carcinoma (NPC) treatment faces challenges due to radioresistance.
- The role of microRNAs (miRNAs) in NPC radioresistance remains largely unexplored.
- miR-23a was identified as downregulated in radioresistant NPC cells.
Purpose of the Study:
- To investigate the function and mechanism of miR-23a in NPC radioresistance.
- To determine if miR-23a can serve as a prognostic biomarker for NPC patients.
- To explore the therapeutic potential of targeting the miR-23a pathway.
Main Methods:
- Microarray analysis to identify differentially expressed miRNAs.
- In vitro radioresponse assays in NPC cells.
- In vivo studies using a mouse xenograft model.
- Analysis of miR-23a, IL-8, and phospho-Stat3 levels in patient tissues.
Main Results:
- miR-23a was frequently downregulated in radioresistant NPC tissues and correlated with poor survival.
- Restoration of miR-23a expression increased NPC cell radiosensitivity in vitro.
- Therapeutic administration of miR-23a agomir sensitized NPC xenografts to irradiation in vivo.
- Reduced miR-23a promoted radioresistance by activating the IL-8/Stat3 signaling pathway.
- IL-8 and phospho-Stat3 levels were elevated in radioresistant tissues and inversely correlated with miR-23a levels.
Conclusions:
- miR-23a is a critical determinant of NPC radioresponse and a prognostic predictor.
- Decreased miR-23a enhances NPC radioresistance via the IL-8/Stat3 signaling axis.
- Targeting the miR-23a/IL-8/Stat3 signaling pathway holds therapeutic potential for NPC radiosensitization.
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