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Erschienen in: Angiogenesis 3/2019

15.04.2019 | Original Paper

RETRACTED ARTICLE: Cancer-derived exosomal miR-221-3p promotes angiogenesis by targeting THBS2 in cervical squamous cell carcinoma

verfasst von: Xiang-Guang Wu, Chen-Fei Zhou, Yan-Mei Zhang, Rui-Ming Yan, Wen-Fei Wei, Xiao-Jing Chen, Hong-Yan Yi, Luo-Jiao Liang, Liang-sheng Fan, Li Liang, Sha Wu, Wei Wang

Erschienen in: Angiogenesis | Ausgabe 3/2019

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Abstract

Aims

Recently, cancer-derived exosomes were shown to have pro-metastasis function in cancer, but the mechanism remains unclear. Angiogenesis is essential for tumor progression and is a great promising therapeutic target for advanced cervical cancer. Here, we investigated the role of cervical cancer cell-secreted exosomal miR-221-3p in tumor angiogenesis.

Methods and results

miR-221-3p was found to be closely correlated with microvascular density in cervical squamous cell carcinoma (CSCC) by evaluating the microvascular density with immunohistochemistry and miR-221-3p expression with in situ hybridization in clinical specimens. Using the groups of CSCC cell lines (SiHa and C33A) with miR-221-3p overexpression and silencing, the CSCC exosomes were characterized by electron microscopy, western blotting, and fluorescence microscopy. The enrichment of miR-221-3p in CSCC exosomes and its transfer into human umbilical vein endothelial cells (HUVECs) were confirmed by qRT-PCR. CSCC exosomal miR-221-3p promoted angiogenesis in vitro in Matrigel tube formation assay, spheroid sprouting assay, migration assay, and wound healing assay. Then, exosome intratumoral injection indicated that CSCC exosomal miR-221-3p promoted tumor growth in vivo. Thrombospondin-2 (THBS2) was bioinformatically predicted to be a direct target of miR-221-3p, and this was verified by using the in vitro and in vivo experiments described above. Additionally, overexpression of THBS2 in HUVECs rescued the angiogenic function of miR-221-3p.

Conclusions

Our results suggest that CSCC exosomes transport miR-221-3p from cancer cells to vessel endothelial cells and promote angiogenesis by downregulating THBS2. Therefore, CSCC-derived exosomal miR-221-3p could be a possible novel diagnostic biomarker and therapeutic target for CSCC progression.
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Metadaten
Titel
RETRACTED ARTICLE: Cancer-derived exosomal miR-221-3p promotes angiogenesis by targeting THBS2 in cervical squamous cell carcinoma
verfasst von
Xiang-Guang Wu
Chen-Fei Zhou
Yan-Mei Zhang
Rui-Ming Yan
Wen-Fei Wei
Xiao-Jing Chen
Hong-Yan Yi
Luo-Jiao Liang
Liang-sheng Fan
Li Liang
Sha Wu
Wei Wang
Publikationsdatum
15.04.2019
Verlag
Springer Netherlands
Erschienen in
Angiogenesis / Ausgabe 3/2019
Print ISSN: 0969-6970
Elektronische ISSN: 1573-7209
DOI
https://doi.org/10.1007/s10456-019-09665-1

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