Journal of cellular physiology, 2019-03, Vol.234 (3), p.2943-2953
2019
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- Autor(en) / Beteiligte
- Titel
- Loss of exosomal miR‐148b from cancer‐associated fibroblasts promotes endometrial cancer cell invasion and cancer metastasis
- Ist Teil von
- Journal of cellular physiology, 2019-03, Vol.234 (3), p.2943-2953
- Ort / Verlag
- United States: Wiley Subscription Services, Inc
- Erscheinungsjahr
- 2019
- Quelle
- Wiley Blackwell Single Titles
- Beschreibungen/Notizen
- Cancer‐associated fibroblasts (CAFs) play crucial roles in tumor progression, given the dependence of cancer cells on stromal support. Therefore, understanding how CAFs communicate with endometrial cancer cell in tumor environment is important for endometrial cancer therapy. Exosomes, which contain proteins and noncoding RNA, are identified as an important mediator of cell–cell communication. However, the function of exosomes in endometrial cancer metastasis remains poorly understood. In the current study we found that CAF‐derived exosomes significantly promoted endometrial cancer cell invasion comparing to those from normal fibroblasts (NFs). We identified a significant decrease of miR‐148b in CAFs and CAFs‐derived exosomes. By exogenously transfect microRNAs, we demonstrated that miR‐148b could be transferred from CAFs to endometrial cancer cell through exosomes. In vitro and in vivo studies further revealed that miR‐148b functioned as a tumor suppressor by directly binding to its downstream target gene, DNMT1 to suppress endometrial cancer metastasis. In endometrial cancer DNMT1 presented a potential role in enhancing cancer cell metastasis by inducing epithelial–mesenchymal transition (EMT). Therefore, downregulated miR‐148b induced EMT of endometrial cancer cell as a result of relieving the suppression of DNMT1. Taken together, these results suggest that CAFs‐mediated endometrial cancer progression is partially related to the loss of miR‐148b in the exosomes of CAFs and promoting the transfer of stromal cell‐derived miR‐148b might be a potential treatment to prevent endometrial cancer progression. miR‐148b promotes endometrial cancer cell invasion and metastasis
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0021-9541eISSN: 1097-4652DOI: 10.1002/jcp.27111Titel-ID: cdi_proquest_miscellaneous_2094431700
- Format
- –
- Schlagworte
- Cancer, cancer metastasis, Cancer-Associated Fibroblasts - metabolism, Cancer-Associated Fibroblasts - pathology, cancer‐associated fibroblasts, Cell interactions, Cell Line, Tumor, Cell Movement - genetics, Cell Proliferation - genetics, Dependence, Disease Progression, DNA (Cytosine-5-)-Methyltransferase 1 - genetics, DNMT1 protein, Endometrial cancer, endometrial cancer cell, Endometrial Neoplasms - genetics, Endometrial Neoplasms - pathology, Endometrium, Epithelial-Mesenchymal Transition - genetics, exosome, Exosomes, Exosomes - genetics, Female, Fibroblasts, Gene Expression Regulation, Neoplastic - genetics, Hormone replacement therapy, Humans, In vivo methods and tests, Kaplan-Meier Estimate, Mesenchyme, Metastases, Metastasis, MicroRNAs - genetics, miRNA, miR‐148b, Neoplasm Invasiveness - genetics, Neoplasm Invasiveness - pathology, Neoplasm Metastasis, Proteins, Ribonucleic acid, RNA, Signal Transduction - genetics, Therapeutic applications, Tumor suppressor genes, Tumors