Exosome-transmitted circ IFNGR2 Modulates Ovarian Cancer Metastasis via miR-378/ST5 Axis
Cancer-associated fibroblasts (CAFs)-derived exosomes have emerged as a key driver of ovarian cancer (OVCA) tumor progression. The mechanisms behind the specific circular RNA (circRNA) activity encapsulated by CAF-generated exosomes (CAF-exo) requires to be elucidated. Herein, this study selected sp...
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Veröffentlicht in: | Molecular and cellular biology 2023-01, Vol.43 (1), p.22-42 |
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Zusammenfassung: | Cancer-associated fibroblasts (CAFs)-derived exosomes have emerged as a key driver of ovarian cancer (OVCA) tumor progression. The mechanisms behind the specific circular RNA (circRNA) activity encapsulated by CAF-generated exosomes (CAF-exo) requires to be elucidated. Herein, this study selected specific circRNA (hsa_circ
) molecules and aimed to clarify novel function of CAF-derived exosomal circ
on growth, and metastasis of OVCA cells. In this study, we clarified that the exosomes of CAFs originating from human ovarian cancer hindered tumor cell proliferation, metastasis and EMT in vitro. Interestingly, CAFs directly transferred exosomes into OVCA cells to enrich intracellular circ
levels. Biologically, activation of exosomal circ
blocked cell proliferation, metastasis and EMT. Mechanistically, enhanced circ
activated the miR-378/ST5 axis and directly inhibited the malignant evolution of tumor cells. Furthermore, rescue experiments evidenced that circ
and ST5 were two essential participants in OVCA, concretely manifested in the co-culture of OVCA cells with exosomes that reversed the effects of intracellular circ
and ST5 depletion. Finally, we observed that CAF-exo treatment hindered tumor growth and increased the size and number of metastatic nodules in mice. Our study revealed a previously unknown regulatory pathway whereby CAFs-derived exosomes delivered circ
and inhibited the malignant progression of OVCA by circ
/miR-378/ST5 axis. |
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ISSN: | 1098-5549 1098-5549 |
DOI: | 10.1080/10985549.2022.2160605 |