Department of Urology, The First Affiliated Hospital of Bengbu Medical University, No. 287, Changhuai Road, Longzi Lake District, Bengbu, 233004, Anhui, People's Republic of China.
Department of Oncology, The First Affiliated Hospital of Bengbu Medical University, No. 287, Changhuai Road, Longzi Lake District, Bengbu, 233004, Anhui, People's Republic of China.
Hum Cell. 2024 Nov 30;38(1):23. doi: 10.1007/s13577-024-01155-x.
The N6-methyladenine (m6A) modification is the most common modification of messenger RNAs in eukaryotes and has crucial roles in multiple cancers, including bladder cancer (BLCA). This paper aimed to probe the molecular mechanism of zinc-finger CCCH-type containing 13 (ZC3H13)-mediated N6-methyladenine (m6A) modification in BLCA progression via autophagy. Differential expression of ZC3H13 in BLCA was analyzed by the bioinformatics database. ZC3H13 expression in BLCA tissues and cell lines was determined, and malignant behaviors of BLCA cells were examined in vitro and in vivo. ZC3H13 was decreased in BLCA tissues and cell lines relative to adjacent tissues and normal uroepithelial cells. ZC3H13 overexpression restricted BLCA cell growth in vitro and curbed BLCA development in vivo. ZC3H13 promoted the mRNA stability of paraja ring finger 2 (PJA2) through m6A modification, leading to the ubiquitination degradation of the kinase suppressor of Ras 1 (KSR1). Knockdown of PJA2 and overexpression of KSR1 reversed the inhibitory effect of ZC3H13 on BLCA progression. ZC3H13 degraded KSR1 through m6A modification of PJA2, promoted cell autophagy, and repressed BLCA progression. Overall, ZC3H13 promotes the mRNA stability of PJA2 through m6A modification to degrade KSR1, thereby promoting autophagy in BLCA.
N6-甲基腺嘌呤（m6A）修饰是真核生物信使 RNA 中最常见的修饰，在多种癌症中具有重要作用，包括膀胱癌（BLCA）。本文旨在通过自噬探讨锌指 CCCH 型包含 13（ZC3H13）介导的 BLCA 进展中 N6-甲基腺嘌呤（m6A）修饰的分子机制。通过生物信息学数据库分析 BLCA 中 ZC3H13 的差异表达。测定 BLCA 组织和细胞系中 ZC3H13 的表达，并在体外和体内检测 BLCA 细胞的恶性行为。与相邻组织和正常尿路上皮细胞相比，BLCA 组织和细胞系中 ZC3H13 的表达降低。ZC3H13 过表达限制了 BLCA 细胞在体外的生长，并抑制了 BLCA 细胞在体内的发育。ZC3H13 通过 m6A 修饰促进了 paraja 环指 2（PJA2）的 mRNA 稳定性，导致 Ras 激酶抑制剂 1（KSR1）的泛素化降解。PJA2 的敲低和 KSR1 的过表达逆转了 ZC3H13 对 BLCA 进展的抑制作用。ZC3H13 通过 PJA2 的 m6A 修饰降解 KSR1，促进细胞自噬，抑制 BLCA 进展。总之，ZC3H13 通过 m6A 修饰促进 PJA2 的 mRNA 稳定性，从而降解 KSR1，促进 BLCA 中的自噬。
