ZC3H13 promotes autophagy in bladder cancer through m6A methylation modification of PJA2 and ubiquitination of KSR1

• Published in: Human cell : official journal of Human Cell Research Society 2024-11, Vol.38 (1), p.23, Article 23
• Main Authors: Liu, Beibei, Chen, Mengjie, Liang, Yujie, Mei, Zhijie, Sun, Wei, Gao, Wuyue, Zhang, Tiantian, Wang, Rui, Guo, Yuanyuan
• Format: Article
• Language: English
• Subjects: Adenine - analogs & derivatives; Adenine - pharmacology; Autophagy; Autophagy - genetics; Bioinformatics; Biomedical and Life Sciences; Bladder cancer; Cell Biology; Cell Line, Tumor; Gene Expression - genetics; Gynecology; Humans; Life Sciences; Methylation; Molecular modelling; mRNA stability; N6-methyladenosine; Oncology; Reproductive Medicine; Research Article; RNA modification; RNA Stability - genetics; Stem Cells; Surgery; Transcription Factors - genetics; Transcription Factors - metabolism; Ubiquitination; Ubiquitination - genetics; Urinary Bladder Neoplasms - genetics; Urinary Bladder Neoplasms - metabolism; Urinary Bladder Neoplasms - pathology; Zinc finger proteins
• ISSN: 1749-0774; 0914-7470; 1749-0774
• 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.