The inhibition of ZC3H13 attenuates G2/M arrest and apoptosis by alleviating NABP1 m6A modification in cisplatin-induced acute kidney injury.

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Tác giả: Xiaoting Fan, Ying Gao, Zhijuan Kong, Shangwei Lu, Zhimei Lv, Qinghao Sheng, Hong Su, Rong Wang, Meilin Yang, Qun Yu

Ngôn ngữ: eng

Ký hiệu phân loại:

Thông tin xuất bản: Switzerland : Cellular and molecular life sciences : CMLS , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 549159

Acute kidney injury (AKI) is a clinical syndrome caused by various etiologies and causes a rapid decline in renal function in a short period of time. The most common internal modification of mRNAs is the N6-methyladenosine (m6A) modification, which is important for controlling gene expressions. However, the role of m6A modification in AKI is largely unknown. Here, we characterized the role of zinc finger CCCH-type containing 13 (ZC3H13), which is a type of m6A methyltransferases, in cisplatin-induced AKI mouse model and a cisplatin-treated human proximal tubular epithelial cell line (HK2 cells). The ZC3H13 knockdown attenuated the G2/M cell cycle arrest and apoptosis in HK2 cells. In the ZC3H13-overexpressed HK2 cells, the opposite was true. In the presence of cisplatin, mice with the AAV9-mediated silencing of ZC3H13 exhibited milder cell cycle arrest, apoptosis, and renal injury. In addition, we identified nucleic acid binding protein 1 (NABP1) as a target of ZC3H13, which was verified by knocking down and overexpressing ZC3H13 in HK2 cells. Moreover, we confirmed that the ZC3H13-mediated m6A modification stabilized NABP1 mRNA and was discriminated by insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1). In conclusion, ZC3H13 promoted the m6A modification of NABP1 and enhanced its mRNA stability through an IGF2BP1-dependent mechanism. The inhibition of ZC3H13 alleviated the G2/M cell cycle arrest, apoptosis and kidney injury by affecting the expression of NABP1. These results show that the ZC3H13/NABP1 axis is a promising AKI treatment target.
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