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<p>Background: Cataracts are a significant cause of vision loss, adversely affecting the quality of human life. Numerous studies have reported that lens epithelial cells (LECs) play a crucial role in age-related cataract (ARC). However, the roles of carboxypeptidase B 1 (CPB1) and transcription factor BTB and CNC homologue 2 (BACH2) in the pathogenesis of ARC remain unclear. In this study, we aim to explore the contributions of CPB1 and BACH2 to the development of ARC. Methods: The Gene Expression Omnibus (GEO) was utilized to screen for differentially expressed genes. mRNA and protein levels were assessed using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot analysis. Flow cytometry was conducted to analyze apoptosis. The levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), and malondialdehyde (MDA) were measured using a commercial kit. Dual-luciferase reporter assays and chromatin immunoprecipitation (CHIP) were performed to investigate the interaction between CPB1 and BACH2. The methylation site of BACH2 was analyzed using the RNA-protein binding sites prediction suite and the sequence-based RNA adenosine methylation site predictor suite. Methylated RNA immunoprecipitation (Me-RIP) was employed to detect m6A modification level of BACH2. Results: In ARC and H<sub>2</sub>O<sub>2</sub>-induced human lens epithelial cells (HLECs), CPB1, BACH2, and METTL3 were found to be up-regulated. Silencing CPB1 reduced apoptosis and MDA levels while enhancing the activities of SOD and GSH-PX in H<sub>2</sub>O<sub>2</sub>-induced HLECs. Additionally, CPB1 was shown to bind to BACH2, and knockdown of BACH2 attenuated apoptosis and oxidative stress in H<sub>2</sub>O<sub>2</sub>-induced HLECs by targeting CPB1. Notably, METTL3 promoted the BACH2 expression by enhancing CPB1 expression in H<sub>2</sub>O<sub>2</sub>-induced HLECs. Finally, silencing METTL3 inhibited apoptosis and oxidative stress in H<sub>2</sub>O<sub>2</sub>-induced HLECs by hampering BACH2 expression. Conclusions: METTL3 facilitates apoptosis and oxidative stress in H<sub>2</sub>O<sub>2</sub>-induced HLECs by promoting the modification of BACH2 and CPB1 expression.</p>

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METTL3 mediates CPB1 expression by regulating transcription factor BACH2 to promote apoptosis and oxidative stress of lens epithelial cells

  • 期刊论文

  • 发表日期：

    2025年2月21日

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  • Zhangxing Sheng,
  • Yu Pan,
  • Liqin Shao,
  • Yihui Bao

摘要

Background: Cataracts are a significant cause of vision loss, adversely affecting the quality of human life. Numerous studies have reported that lens epithelial cells (LECs) play a crucial role in age-related cataract (ARC). However, the roles of carboxypeptidase B 1 (CPB1) and transcription factor BTB and CNC homologue 2 (BACH2) in the pathogenesis of ARC remain unclear. In this study, we aim to explore the contributions of CPB1 and BACH2 to the development of ARC. Methods: The Gene Expression Omnibus (GEO) was utilized to screen for differentially expressed genes. mRNA and protein levels were assessed using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot analysis. Flow cytometry was conducted to analyze apoptosis. The levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), and malondialdehyde (MDA) were measured using a commercial kit. Dual-luciferase reporter assays and chromatin immunoprecipitation (CHIP) were performed to investigate the interaction between CPB1 and BACH2. The methylation site of BACH2 was analyzed using the RNA-protein binding sites prediction suite and the sequence-based RNA adenosine methylation site predictor suite. Methylated RNA immunoprecipitation (Me-RIP) was employed to detect m6A modification level of BACH2. Results: In ARC and H2O2-induced human lens epithelial cells (HLECs), CPB1, BACH2, and METTL3 were found to be up-regulated. Silencing CPB1 reduced apoptosis and MDA levels while enhancing the activities of SOD and GSH-PX in H2O2-induced HLECs. Additionally, CPB1 was shown to bind to BACH2, and knockdown of BACH2 attenuated apoptosis and oxidative stress in H2O2-induced HLECs by targeting CPB1. Notably, METTL3 promoted the BACH2 expression by enhancing CPB1 expression in H2O2-induced HLECs. Finally, silencing METTL3 inhibited apoptosis and oxidative stress in H2O2-induced HLECs by hampering BACH2 expression. Conclusions: METTL3 facilitates apoptosis and oxidative stress in H2O2-induced HLECs by promoting the modification of BACH2 and CPB1 expression.