Scholarlink

Objective <p>This study explores the mechanism of long non-coding RNA ITGB2-AS1 regulating ferroptosis in non-small-cell lung cancer (NSCLC) cells.</p> Methods <p>ITGB2-AS1, HOXB8, and USP11 expressions in NSCLC cells were assessed using RT-qPCR and Western blotting. Following ITGB2-AS1 knockdown, intracellular levels of iron ions, glutathione (GSH), malondialdehyde (MDA), and reactive oxygen species (ROS), along with the expressions of ACSL4 and GPX4, were measured. Lipid peroxidation was quantified using thiobarbituric acid reactive substances (TBARS) assay. The subcellular localization of ITGB2-AS1 was determined through nuclear and cytoplasmic fractionation. RNA immunoprecipitation (RIP) and RNA pull-down assays were conducted to confirm the interaction between ITGB2-AS1 and MLL1. Chromatin immunoprecipitation (ChIP) was employed to examine MLL1 and H3K4me3 enrichment at the HOXB8 promoter. Furthermore, ChIP and dual-luciferase reporter assays were used to investigate the binding of HOXB8 to the USP11 promoter.</p> Results <p>ITGB2-AS1, HOXB8, and USP11 were highly expressed in NSCLC cells. Silencing ITGB2-AS1 led to a marked decrease in GSH levels and GPX4 expression, elevated intracellular iron ions, TBARS, MDA, ROS, and increased ACSL4 expression. Mechanistically, ITGB2-AS1 facilitated the recruitment of MLL1 to the HOXB8 promoter, enhancing H3K4me3 histone modification, upregulating HOXB8 expression, and promoting USP11 expression. The ferroptosis-inducing effect observed with ITGB2-AS1 knockdown was reversed by overexpression of either HOXB8 or USP11.</p> Conclusion <p>ITGB2-AS1 facilitates the recruitment of MLL1 to the HOXB8 promoter, enhancing H3K4me3 histone modification and upregulating HOXB8 expression, which in turn transcriptionally activates USP11 expression, ultimately suppressing ferroptosis in NSCLC cells.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

The regulatory role and molecular mechanism of lncRNA ITGB2-AS1 in ferroptosis of non-small cell lung cancer cells

  • 期刊论文

  • 发表日期：

    2025年8月27日

查看全文
  • Qichang Jiang,
  • Yan Lv,
  • Yang Liu,
  • Longfeng Gu,
  • Hui Wang,
  • Yanmiao Yang

摘要

Objective

This study explores the mechanism of long non-coding RNA ITGB2-AS1 regulating ferroptosis in non-small-cell lung cancer (NSCLC) cells.

Methods

ITGB2-AS1, HOXB8, and USP11 expressions in NSCLC cells were assessed using RT-qPCR and Western blotting. Following ITGB2-AS1 knockdown, intracellular levels of iron ions, glutathione (GSH), malondialdehyde (MDA), and reactive oxygen species (ROS), along with the expressions of ACSL4 and GPX4, were measured. Lipid peroxidation was quantified using thiobarbituric acid reactive substances (TBARS) assay. The subcellular localization of ITGB2-AS1 was determined through nuclear and cytoplasmic fractionation. RNA immunoprecipitation (RIP) and RNA pull-down assays were conducted to confirm the interaction between ITGB2-AS1 and MLL1. Chromatin immunoprecipitation (ChIP) was employed to examine MLL1 and H3K4me3 enrichment at the HOXB8 promoter. Furthermore, ChIP and dual-luciferase reporter assays were used to investigate the binding of HOXB8 to the USP11 promoter.

Results

ITGB2-AS1, HOXB8, and USP11 were highly expressed in NSCLC cells. Silencing ITGB2-AS1 led to a marked decrease in GSH levels and GPX4 expression, elevated intracellular iron ions, TBARS, MDA, ROS, and increased ACSL4 expression. Mechanistically, ITGB2-AS1 facilitated the recruitment of MLL1 to the HOXB8 promoter, enhancing H3K4me3 histone modification, upregulating HOXB8 expression, and promoting USP11 expression. The ferroptosis-inducing effect observed with ITGB2-AS1 knockdown was reversed by overexpression of either HOXB8 or USP11.

Conclusion

ITGB2-AS1 facilitates the recruitment of MLL1 to the HOXB8 promoter, enhancing H3K4me3 histone modification and upregulating HOXB8 expression, which in turn transcriptionally activates USP11 expression, ultimately suppressing ferroptosis in NSCLC cells.