Cancer-associated fibroblasts-derived exosomal piR-35462 promotes the progression of oral squamous cell carcinoma via FTO/Twist1 pathway
Abstract Background Cancer-associated fibroblasts (CAFs) represent a crucial component of tumor stroma and play critical roles in cancer progression. However, the role of CAFs derived exosomes in oral squamous cell carcinoma (OSCC) environment is unexplored. PIWI-interacting RNAs (piRNAs) serve as e...
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BMC
2025-05-01
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| Series: | BMC Oral Health |
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| Online Access: | https://doi.org/10.1186/s12903-025-06082-3 |
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| author | Yushan Ye Fan Wu Bowen Li Hanyu Ma Lianxi Mai Yu Peng Xiaodi Feng Xiao Tan Min Fu Yongmei Tan Tianjun Lan Ruixin Wang Siqi Ren Jinsong Li Shaohai Chang Shule Xie |
| author_facet | Yushan Ye Fan Wu Bowen Li Hanyu Ma Lianxi Mai Yu Peng Xiaodi Feng Xiao Tan Min Fu Yongmei Tan Tianjun Lan Ruixin Wang Siqi Ren Jinsong Li Shaohai Chang Shule Xie |
| author_sort | Yushan Ye |
| collection | DOAJ |
| description | Abstract Background Cancer-associated fibroblasts (CAFs) represent a crucial component of tumor stroma and play critical roles in cancer progression. However, the role of CAFs derived exosomes in oral squamous cell carcinoma (OSCC) environment is unexplored. PIWI-interacting RNAs (piRNAs) serve as epigenetic effectors in cancer progression and constitute significant compositions of exosomes. Here, we explored the functional mechanism of exosomal piRNAs in OSCC development. Methods We screened exosomal piRNAs derived from CAFs and normal fibroblasts (NFs) and assess their effect on tumor proliferation and metastasis. A nude mouse model was established to assess the impact of exosomal piR-35462 on tumor progression. Results CAFs-derived exosomes showed an enhanced piR-35462 expression and promoted OSCC cell proliferation, migration and invasion. Additionally, elevated piR-35462 expression in OSCC tissues correlates with poor prognosis. Mechanistically, CAFs-derived exosomal piR-35462 increased the expression of fat mass and obesity-associated protein (FTO) in OSCC cells. By inhibiting N6-methyladenosine (m6A) RNA methylation, the overexpression of FTO further enhances the stability and expression levels of Twist1 mRNA, thereby contributing to epithelial-mesenchymal transition (EMT) and tumor progression. In vivo xenograft tumor model also confirmed the same results. Conclusion The achieved outcomes elucidate that CAFs can deliver piR-35462 containing exosomes to OSCC cells and promote OSCC progression via FTO/Twist mediated EMT pathways, and could represent a promising therapeutic target for OSCC. |
| format | Article |
| id | doaj-art-7ae6af2c33c04bd8ad20d5344f32b89e |
| institution | DOAJ |
| issn | 1472-6831 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Oral Health |
| spelling | doaj-art-7ae6af2c33c04bd8ad20d5344f32b89e2025-08-20T03:22:03ZengBMCBMC Oral Health1472-68312025-05-0125111510.1186/s12903-025-06082-3Cancer-associated fibroblasts-derived exosomal piR-35462 promotes the progression of oral squamous cell carcinoma via FTO/Twist1 pathwayYushan Ye0Fan Wu1Bowen Li2Hanyu Ma3Lianxi Mai4Yu Peng5Xiaodi Feng6Xiao Tan7Min Fu8Yongmei Tan9Tianjun Lan10Ruixin Wang11Siqi Ren12Jinsong Li13Shaohai Chang14Shule Xie15Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityDepartment of Pathology, The First Affiliated Hospital, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityDepartment of Stomatology, The First Affiliated Hospital, Medical College of Shantou UniversityGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityGuangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen UniversityAbstract Background Cancer-associated fibroblasts (CAFs) represent a crucial component of tumor stroma and play critical roles in cancer progression. However, the role of CAFs derived exosomes in oral squamous cell carcinoma (OSCC) environment is unexplored. PIWI-interacting RNAs (piRNAs) serve as epigenetic effectors in cancer progression and constitute significant compositions of exosomes. Here, we explored the functional mechanism of exosomal piRNAs in OSCC development. Methods We screened exosomal piRNAs derived from CAFs and normal fibroblasts (NFs) and assess their effect on tumor proliferation and metastasis. A nude mouse model was established to assess the impact of exosomal piR-35462 on tumor progression. Results CAFs-derived exosomes showed an enhanced piR-35462 expression and promoted OSCC cell proliferation, migration and invasion. Additionally, elevated piR-35462 expression in OSCC tissues correlates with poor prognosis. Mechanistically, CAFs-derived exosomal piR-35462 increased the expression of fat mass and obesity-associated protein (FTO) in OSCC cells. By inhibiting N6-methyladenosine (m6A) RNA methylation, the overexpression of FTO further enhances the stability and expression levels of Twist1 mRNA, thereby contributing to epithelial-mesenchymal transition (EMT) and tumor progression. In vivo xenograft tumor model also confirmed the same results. Conclusion The achieved outcomes elucidate that CAFs can deliver piR-35462 containing exosomes to OSCC cells and promote OSCC progression via FTO/Twist mediated EMT pathways, and could represent a promising therapeutic target for OSCC.https://doi.org/10.1186/s12903-025-06082-3Cancer-associated fibroblastsOral squamous cell carcinomaExosomepiRNAEpithelial-mesenchymal transition |
| spellingShingle | Yushan Ye Fan Wu Bowen Li Hanyu Ma Lianxi Mai Yu Peng Xiaodi Feng Xiao Tan Min Fu Yongmei Tan Tianjun Lan Ruixin Wang Siqi Ren Jinsong Li Shaohai Chang Shule Xie Cancer-associated fibroblasts-derived exosomal piR-35462 promotes the progression of oral squamous cell carcinoma via FTO/Twist1 pathway BMC Oral Health Cancer-associated fibroblasts Oral squamous cell carcinoma Exosome piRNA Epithelial-mesenchymal transition |
| title | Cancer-associated fibroblasts-derived exosomal piR-35462 promotes the progression of oral squamous cell carcinoma via FTO/Twist1 pathway |
| title_full | Cancer-associated fibroblasts-derived exosomal piR-35462 promotes the progression of oral squamous cell carcinoma via FTO/Twist1 pathway |
| title_fullStr | Cancer-associated fibroblasts-derived exosomal piR-35462 promotes the progression of oral squamous cell carcinoma via FTO/Twist1 pathway |
| title_full_unstemmed | Cancer-associated fibroblasts-derived exosomal piR-35462 promotes the progression of oral squamous cell carcinoma via FTO/Twist1 pathway |
| title_short | Cancer-associated fibroblasts-derived exosomal piR-35462 promotes the progression of oral squamous cell carcinoma via FTO/Twist1 pathway |
| title_sort | cancer associated fibroblasts derived exosomal pir 35462 promotes the progression of oral squamous cell carcinoma via fto twist1 pathway |
| topic | Cancer-associated fibroblasts Oral squamous cell carcinoma Exosome piRNA Epithelial-mesenchymal transition |
| url | https://doi.org/10.1186/s12903-025-06082-3 |
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