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DNA aptamer S11e recognizes fibrosarcoma and acts as a tumor suppressor

Fibrosarcoma is a serious malignant mesenchymal tumor with strong invasiveness, high recurrence, and poor prognosis. Currently, surgical resection is the main treatment for fibrosarcoma. However, due to the lack of specific biomarkers, the inability to accurately diagnose fibrosarcoma can lead to su...

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Autores principales: Liu, Yunyi, Peng, Cheng, Zhang, Hui, Li, Juan, Ou, Hailong, Sun, Yang, Wen, Chaoqi, Qi, Dan, Hu, Xiaoxiao, Wu, Erxi, Tan, Weihong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: KeAi Publishing 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8897059/
https://www.ncbi.nlm.nih.gov/pubmed/35310383
http://dx.doi.org/10.1016/j.bioactmat.2021.10.011
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author Liu, Yunyi
Peng, Cheng
Zhang, Hui
Li, Juan
Ou, Hailong
Sun, Yang
Wen, Chaoqi
Qi, Dan
Hu, Xiaoxiao
Wu, Erxi
Tan, Weihong
author_facet Liu, Yunyi
Peng, Cheng
Zhang, Hui
Li, Juan
Ou, Hailong
Sun, Yang
Wen, Chaoqi
Qi, Dan
Hu, Xiaoxiao
Wu, Erxi
Tan, Weihong
author_sort Liu, Yunyi
collection PubMed
description Fibrosarcoma is a serious malignant mesenchymal tumor with strong invasiveness, high recurrence, and poor prognosis. Currently, surgical resection is the main treatment for fibrosarcoma. However, due to the lack of specific biomarkers, the inability to accurately diagnose fibrosarcoma can lead to sub-optimal surgical outcomes and decreased survival. Here, we seek to address this translational barrier and we show that DNA aptamer S11e was able to recognize fibrosarcoma cells (HT1080) but not human embryonic lung fibroblast cells with Kd values in the nanomolar range. In addition, we found that S11e discerned tumors in HT1080 xenograft mouse models and tumor tissues from fibrosarcoma patients. Furthermore, we demonstrated that S11e internalized into HT1080 cells independent of the lysosome pathway and located in mitochondria. Moreover, we revealed that S11e promoted the apoptosis of HT1080 cells and inhibited HT1080 cell migration. Finally, we investigated the biologically functional cellular target of S11e using a mass spectrometry approach, and identified that Diablo/SMAC protein is a cellular binding protein of S11e, by interacting to which S11e inhibited HT1080 cell migration and invasion. Taken together, these results provide the evidence that S11e may be useful for early diagnosis, targeted therapy, and prognostication of fibrosarcoma.
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spelling pubmed-88970592022-03-17 DNA aptamer S11e recognizes fibrosarcoma and acts as a tumor suppressor Liu, Yunyi Peng, Cheng Zhang, Hui Li, Juan Ou, Hailong Sun, Yang Wen, Chaoqi Qi, Dan Hu, Xiaoxiao Wu, Erxi Tan, Weihong Bioact Mater Article Fibrosarcoma is a serious malignant mesenchymal tumor with strong invasiveness, high recurrence, and poor prognosis. Currently, surgical resection is the main treatment for fibrosarcoma. However, due to the lack of specific biomarkers, the inability to accurately diagnose fibrosarcoma can lead to sub-optimal surgical outcomes and decreased survival. Here, we seek to address this translational barrier and we show that DNA aptamer S11e was able to recognize fibrosarcoma cells (HT1080) but not human embryonic lung fibroblast cells with Kd values in the nanomolar range. In addition, we found that S11e discerned tumors in HT1080 xenograft mouse models and tumor tissues from fibrosarcoma patients. Furthermore, we demonstrated that S11e internalized into HT1080 cells independent of the lysosome pathway and located in mitochondria. Moreover, we revealed that S11e promoted the apoptosis of HT1080 cells and inhibited HT1080 cell migration. Finally, we investigated the biologically functional cellular target of S11e using a mass spectrometry approach, and identified that Diablo/SMAC protein is a cellular binding protein of S11e, by interacting to which S11e inhibited HT1080 cell migration and invasion. Taken together, these results provide the evidence that S11e may be useful for early diagnosis, targeted therapy, and prognostication of fibrosarcoma. KeAi Publishing 2021-10-15 /pmc/articles/PMC8897059/ /pubmed/35310383 http://dx.doi.org/10.1016/j.bioactmat.2021.10.011 Text en © 2021 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Liu, Yunyi
Peng, Cheng
Zhang, Hui
Li, Juan
Ou, Hailong
Sun, Yang
Wen, Chaoqi
Qi, Dan
Hu, Xiaoxiao
Wu, Erxi
Tan, Weihong
DNA aptamer S11e recognizes fibrosarcoma and acts as a tumor suppressor
title DNA aptamer S11e recognizes fibrosarcoma and acts as a tumor suppressor
title_full DNA aptamer S11e recognizes fibrosarcoma and acts as a tumor suppressor
title_fullStr DNA aptamer S11e recognizes fibrosarcoma and acts as a tumor suppressor
title_full_unstemmed DNA aptamer S11e recognizes fibrosarcoma and acts as a tumor suppressor
title_short DNA aptamer S11e recognizes fibrosarcoma and acts as a tumor suppressor
title_sort dna aptamer s11e recognizes fibrosarcoma and acts as a tumor suppressor
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8897059/
https://www.ncbi.nlm.nih.gov/pubmed/35310383
http://dx.doi.org/10.1016/j.bioactmat.2021.10.011
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