4.2 Article

Exosomal miR-193b-3p Contributes to Cisplatin Sensitivity in Seminoma by Targeting ZBTB7A

Journal

TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE
Volume 258, Issue 4, Pages 309-317

Publisher

TOHOKU UNIV MEDICAL PRESS
DOI: 10.1620/tjem.2022.J080

Keywords

cisplatin; exosomes; miR-193b-3p; seminoma; ZBTB7A

Funding

  1. Hunan Natural Science Foundation [2019JJ80008]

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Exosomes carrying miR-193b-3p can modulate the chemosensitivity of TCam-2 cells to cisplatin by reducing DNA damage, enhancing cell growth, and regulating apoptosis and cell cycle progression through the ZBTB7A signaling pathway.
A previous study confirmed that miRNAs play an important role in the chemosensitivity of seminoma. Increasing evidence reveals that exosomes participate in the regulation of cisplatin resistance by carrying miRNAs. In this study, we further explored whether exosomes regulated the chemosensitivity of seminoma TCam-2 cells to cisplatin. Initially, cisplatin-resistant TCam-2 cells were induced. Our results revealed that exosomes from cisplatin-resistant TCam-2 cells (rExos) could affect the viability of TCam-2 cells in the context of cisplatin treatment through regulation of both cell apoptosis and the cell cycle. Meanwhile, the levels of. -H2AX were negatively modulated by rExos, which indicated that rExos could decrease the DNA damage from cisplatin. Furthermore, miR-193b-3p was enriched in rExos, and exosomal miR-193b-3p enhanced the proliferative ability of TCam-2 cells under cisplatin treatment. Mechanistically, exosomal miR- 193b-3p targets ZBTB7A, which further decreases apoptosis and promotes cell cycle progression. Taken together, these findings indicate that exosomal miR- 193b-3p regulates the chemosensitivity of TCam-2 cells to cisplatin through ZBTB7A signaling and could be a promising drug target for patients with chemoresistant seminoma.

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