Exosomal miR-196a derived from cancer-associated fibroblasts confers cisplatin resistance in head and neck cancer through targeting CDKN1B and ING5
Abstract Background Cisplatin resistance is a major challenge for advanced head and neck cancer (HNC). Understanding the underlying mechanisms and developing effective strategies against cisplatin resistance are highly desired in the clinic. However, how tumor stroma modulates HNC growth and chemore...
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| Format: | Article |
| Language: | English |
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BMC
2019-01-01
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| Series: | Genome Biology |
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| Online Access: | http://link.springer.com/article/10.1186/s13059-018-1604-0 |
| _version_ | 1828337438493245440 |
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| author | Xing Qin Haiyan Guo Xiaoning Wang Xueqin Zhu Ming Yan Xu Wang Qin Xu Jianbo Shi Eryi Lu Wantao Chen Jianjun Zhang |
| author_facet | Xing Qin Haiyan Guo Xiaoning Wang Xueqin Zhu Ming Yan Xu Wang Qin Xu Jianbo Shi Eryi Lu Wantao Chen Jianjun Zhang |
| author_sort | Xing Qin |
| collection | DOAJ |
| description | Abstract Background Cisplatin resistance is a major challenge for advanced head and neck cancer (HNC). Understanding the underlying mechanisms and developing effective strategies against cisplatin resistance are highly desired in the clinic. However, how tumor stroma modulates HNC growth and chemoresistance is unclear. Results We show that cancer-associated fibroblasts (CAFs) are intrinsically resistant to cisplatin and have an active role in regulating HNC cell survival and proliferation by delivering functional miR-196a from CAFs to tumor cells via exosomes. Exosomal miR-196a then binds novel targets, CDKN1B and ING5, to endow HNC cells with cisplatin resistance. Exosome or exosomal miR-196a depletion from CAFs functionally restored HNC cisplatin sensitivity. Importantly, we found that miR-196a packaging into CAF-derived exosomes might be mediated by heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1). Moreover, we also found that high levels of plasma exosomal miR-196a are clinically correlated with poor overall survival and chemoresistance. Conclusions The present study finds that CAF-derived exosomal miR-196a confers cisplatin resistance in HNC by targeting CDKN1B and ING5, indicating miR-196a may serve as a promising predictor of and potential therapeutic target for cisplatin resistance in HNC. |
| first_indexed | 2024-04-13T22:15:35Z |
| format | Article |
| id | doaj.art-76511cf60d0940648e6cbfbd0fe595dd |
| institution | Directory Open Access Journal |
| issn | 1474-760X |
| language | English |
| last_indexed | 2024-04-13T22:15:35Z |
| publishDate | 2019-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Genome Biology |
| spelling | doaj.art-76511cf60d0940648e6cbfbd0fe595dd2022-12-22T02:27:34ZengBMCGenome Biology1474-760X2019-01-0120112110.1186/s13059-018-1604-0Exosomal miR-196a derived from cancer-associated fibroblasts confers cisplatin resistance in head and neck cancer through targeting CDKN1B and ING5Xing Qin0Haiyan Guo1Xiaoning Wang2Xueqin Zhu3Ming Yan4Xu Wang5Qin Xu6Jianbo Shi7Eryi Lu8Wantao Chen9Jianjun Zhang10Department of Oral and Maxillofacial-Head & Neck Oncology, Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Clinical Laboratory, Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Oral and Maxillofacial-Head & Neck Oncology, Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Oral and Maxillofacial-Head & Neck Oncology, Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Oral and Maxillofacial-Head & Neck Oncology, Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Oral and Maxillofacial-Head & Neck Oncology, Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Oral and Maxillofacial-Head & Neck Oncology, Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Oral and Maxillofacial-Head & Neck Oncology, Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Stomatology, Renji Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Oral and Maxillofacial-Head & Neck Oncology, Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineDepartment of Oral and Maxillofacial-Head & Neck Oncology, Ninth People’s Hospital, Shanghai Jiao Tong University School of MedicineAbstract Background Cisplatin resistance is a major challenge for advanced head and neck cancer (HNC). Understanding the underlying mechanisms and developing effective strategies against cisplatin resistance are highly desired in the clinic. However, how tumor stroma modulates HNC growth and chemoresistance is unclear. Results We show that cancer-associated fibroblasts (CAFs) are intrinsically resistant to cisplatin and have an active role in regulating HNC cell survival and proliferation by delivering functional miR-196a from CAFs to tumor cells via exosomes. Exosomal miR-196a then binds novel targets, CDKN1B and ING5, to endow HNC cells with cisplatin resistance. Exosome or exosomal miR-196a depletion from CAFs functionally restored HNC cisplatin sensitivity. Importantly, we found that miR-196a packaging into CAF-derived exosomes might be mediated by heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1). Moreover, we also found that high levels of plasma exosomal miR-196a are clinically correlated with poor overall survival and chemoresistance. Conclusions The present study finds that CAF-derived exosomal miR-196a confers cisplatin resistance in HNC by targeting CDKN1B and ING5, indicating miR-196a may serve as a promising predictor of and potential therapeutic target for cisplatin resistance in HNC.http://link.springer.com/article/10.1186/s13059-018-1604-0ExosomeCancer-associated fibroblastsmiR-196aCisplatin resistanceHead and neck cancerCDKN1B |
| spellingShingle | Xing Qin Haiyan Guo Xiaoning Wang Xueqin Zhu Ming Yan Xu Wang Qin Xu Jianbo Shi Eryi Lu Wantao Chen Jianjun Zhang Exosomal miR-196a derived from cancer-associated fibroblasts confers cisplatin resistance in head and neck cancer through targeting CDKN1B and ING5 Genome Biology Exosome Cancer-associated fibroblasts miR-196a Cisplatin resistance Head and neck cancer CDKN1B |
| title | Exosomal miR-196a derived from cancer-associated fibroblasts confers cisplatin resistance in head and neck cancer through targeting CDKN1B and ING5 |
| title_full | Exosomal miR-196a derived from cancer-associated fibroblasts confers cisplatin resistance in head and neck cancer through targeting CDKN1B and ING5 |
| title_fullStr | Exosomal miR-196a derived from cancer-associated fibroblasts confers cisplatin resistance in head and neck cancer through targeting CDKN1B and ING5 |
| title_full_unstemmed | Exosomal miR-196a derived from cancer-associated fibroblasts confers cisplatin resistance in head and neck cancer through targeting CDKN1B and ING5 |
| title_short | Exosomal miR-196a derived from cancer-associated fibroblasts confers cisplatin resistance in head and neck cancer through targeting CDKN1B and ING5 |
| title_sort | exosomal mir 196a derived from cancer associated fibroblasts confers cisplatin resistance in head and neck cancer through targeting cdkn1b and ing5 |
| topic | Exosome Cancer-associated fibroblasts miR-196a Cisplatin resistance Head and neck cancer CDKN1B |
| url | http://link.springer.com/article/10.1186/s13059-018-1604-0 |
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