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Extracellular vesicles-encapsulated microRNA-10a-5p shed from cancer-associated fibroblast facilitates cervical squamous cell carcinoma cell angiogenesis and tumorigenicity via Hedgehog signaling pathway
- Source :
- Cancer Gene Therapy. 28:529-542
- Publication Year :
- 2020
- Publisher :
- Springer Science and Business Media LLC, 2020.
-
Abstract
- Cancer-associated fibroblast (CAF) secretes extracellular vesicle (EV)-encapsulated microRNAs (miRNAs) which have been underlined great promise for therapeutic target for diseases and cancers. Our study aimed to explore the role of EV-encapsulated miR-10a-5p from CAFs in angiogenesis in cervical cancer. Expression of miR-10a-5p in clinical samples of cervical cancer and cancer cells was detected by in situ hybridization and RT-qPCR. Results demonstrated that miR-10a-5p expression was upregulated in both cancer tissues and cells. CAFs and normal fibroblasts (NFs) from cervical cancer patient tissues were characterized under transmission electron microscopy, followed by EV isolation from CAFs. The EVs labeled with PKH67 were cultured with cervical squamous cell carcinoma (CSCC) cell line (SiHa) and HUVECs. Data indicated that CAF-EVs were internalized by cancer cells and promoted cell proliferation and tube formation. CAF-EVs then were transfected with miR-10a-5p inhibitor and then injected into nude mice. While injection of CAF-EVs promoted tumor growth and increased VEGFR and CD31 expression level, miR-10a-5p inhibitor-treated CAF-EVs resulted in decreased tumor volume and amount of vessel around tumor. Of note, dual-luciferase reporter gene assay and bioinformatic analysis indicated TBX5 as a target gene of miR-10a-5p. Moreover, EV-derived miR-10a-5p promoted angiogenesis in vivo and in vitro through activation of Hedgehog signaling via downregulation of TBX5. Taken altogether, miR-10a-5p in CAF-EVs promoted CSCC cell angiogenesis and tumorigenicity via activation of Hh signaling by inhibition of TBX5, providing insight into novel treatment based on miR-10a-5p against CSCC.
- Subjects :
- 0301 basic medicine
Cancer Research
Angiogenesis
Cell
Mice, Nude
Uterine Cervical Neoplasms
Apoptosis
Extracellular Vesicles
Mice
03 medical and health sciences
0302 clinical medicine
Cancer-Associated Fibroblasts
Tumor Cells, Cultured
medicine
Animals
Humans
Hedgehog Proteins
Fibroblast
Molecular Biology
Cell Proliferation
Neovascularization, Pathologic
Cell growth
Chemistry
Cancer
Extracellular vesicle
Prognosis
medicine.disease
Xenograft Model Antitumor Assays
Hedgehog signaling pathway
Gene Expression Regulation, Neoplastic
MicroRNAs
030104 developmental biology
medicine.anatomical_structure
030220 oncology & carcinogenesis
Cancer cell
Carcinoma, Squamous Cell
Cancer research
Molecular Medicine
Female
Subjects
Details
- ISSN :
- 14765500 and 09291903
- Volume :
- 28
- Database :
- OpenAIRE
- Journal :
- Cancer Gene Therapy
- Accession number :
- edsair.doi.dedup.....60932ffdbb4cf7c95b429ede44cdec37