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

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

Yong Wang,¹ Jianjun Luo,¹ Sheng Hu,¹ Qiong Guo,¹ Xi Guo,¹ Weigang Ren,¹ Qiang Zhou¹ and Yixing Duan¹

¹Department of Urology Surgery, Hunan Provincial People’s Hospital/The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan, China

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 γ-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.

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

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Tohoku J. Exp. Med 2022, 258, 309-317.

Correspondence: Yixing Duan, Department of Urology Surgery, Hunan Provincial People’s Hospital/The First Affiliated Hospital of Hunan Normal University, No. 61, Jiefang West Road, Furong District, Changsha, Hunan 410002, China.

e-mail: dyxhncs@163.com