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Exosome-derived miR-339-5p mediates radiosensitivity by targeting Cdc25A in locally advanced esophageal squamous cell carcinoma
- Source :
- Oncogene; June 2019, Vol. 38 Issue: 25 p4990-5006, 17p
- Publication Year :
- 2019
-
Abstract
- Cancer cells associated with radioresistance are likely to give rise to local recurrence and distant metastatic relapse. However, it remains unclear whether specific miRNAs have direct roles in radioresistance and/or prognosis. In this study, we find that miR-339-5p promotes radiosensitivity, and is downregulated in radioresistant subpopulations of esophageal cancer cells. Notably, miR-339-5p was selectively secreted into blood via exosomes, and that higher serum miR-339-5p levels were positively associated with radiotherapy sensitivity and good survival. Moreover, miR-339-5p expression was downregulated in the T3/T4 stage compared with T1/T2 stage in esophageal squamous cell carcinoma (ESCC) patients (P= 0.04), and low miR-339-5p expression in tissue was significantly associated with poor overall survival (P= 0.036) and disease-free survival (P= 0.037). Overexpression of miR-339-5p enhanced radiosensitivity in vitro and in vivo. Mechanistically, miR-339-5p enhances radiosensitivity by targeting Cdc25A, and is transcriptionally regulated by Runx3. Correlations were observed between miR-339-5p levels and Cdc25A/Runx3 levels in tissue samples. Intriguingly, combined analysis of miR-339-5p expression with Runx3 increased the separation of the survival curves obtained for either gene alone in the TCGA datasets (P= 0.009). Overall, exosome-derived miR-339-5p mediates radiosensitivity through downregulation of Cdc25A, and predicts pathological response to preoperative radiotherapy in locally advanced ESCC, suggesting it could be a promising non-invasive biomarker for facilitating personalized treatments.
Details
- Language :
- English
- ISSN :
- 09509232 and 14765594
- Volume :
- 38
- Issue :
- 25
- Database :
- Supplemental Index
- Journal :
- Oncogene
- Publication Type :
- Periodical
- Accession number :
- ejs49176172
- Full Text :
- https://doi.org/10.1038/s41388-019-0771-0