2021Bioactive MaterialsOpen access

DNA aptamer S11e recognizes fibrosarcoma and acts as a tumor suppressor

Yunyi Liu, Cheng Peng, Hui Zhang, Juan Li, Hailong Ou, Yang Sun, Chaoqi Wen, Dan Qi, Xiaoxiao Hu, Erxi Wu, Weihong Tan

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Abstract

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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What this paper is about

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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Available abstract

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.

Key concepts: HT1080, Fibrosarcoma, Cancer research, Fibroblast, Cell, Biology, Molecular biology, Cell biology

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