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<p>The RNA-binding protein polypyrimidine tract-binding protein 1 (PTBP1) facilitates tumor progression in various cancers by interacting with mRNAs of key oncogenes and tumor suppressors, thereby regulating their mRNA stability, alternative splicing, and protein translation. In this study, we found that​​ PTBP1 knockdown notably inhibited both in vitro cell viability and in vivo tumor growth in endometrial cancer (EC) cells. Elevated PTBP1 protein levels were also observed in endometrial cancer tissues compared to normal endometrial tissues. Transcriptomic sequencing revealed that PTBP1 depletion might impact lipid metabolism and ferroptosis in endometrial cancer cells. Through measurements of intracellular reactive oxygen species (ROS), glutathione (GSH), malondialdehyde (MDA), and Fe<sup>2+</sup> levels, along with the expression of ferroptosis-related genes [acyl-CoA synthetase long-chain family member 4 (ACSL4), NADPH oxidase 1 (NOX1), glutathione peroxidase 4 (GPX4), and heat shock protein 27 (HSP27)], it was demonstrated that PTBP1 knockdown significantly enhances ferroptosis in endometrial cancer cells. Mechanistic studies further indicated that PTBP1 binds to the 5’ untranslated region (UTR) of solute carrier family 7 member 11 (SLC7A11) mRNA, stabilizing it and preserving SLC7A11 protein expression, thus inhibiting ferroptosis. Our study proposes a molecular mechanism by which PTBP1 promotes endometrial cancer progression by suppressing ferroptosis​​, suggesting that PTBP1 may be a promising therapeutic target for endometrial cancer.</p>

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PTBP1 functions as a suppressor of ferroptosis in endometrial carcinoma cells by stabilizing SLC7A11 mRNA

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月28日

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  • Keke Zhu,
  • Ke Zhang,
  • Hui Li,
  • Yao Shen,
  • Lu Wang,
  • Qinghong Hu,
  • Hanwen Xing,
  • Liping Han

摘要

The RNA-binding protein polypyrimidine tract-binding protein 1 (PTBP1) facilitates tumor progression in various cancers by interacting with mRNAs of key oncogenes and tumor suppressors, thereby regulating their mRNA stability, alternative splicing, and protein translation. In this study, we found that​​ PTBP1 knockdown notably inhibited both in vitro cell viability and in vivo tumor growth in endometrial cancer (EC) cells. Elevated PTBP1 protein levels were also observed in endometrial cancer tissues compared to normal endometrial tissues. Transcriptomic sequencing revealed that PTBP1 depletion might impact lipid metabolism and ferroptosis in endometrial cancer cells. Through measurements of intracellular reactive oxygen species (ROS), glutathione (GSH), malondialdehyde (MDA), and Fe2+ levels, along with the expression of ferroptosis-related genes [acyl-CoA synthetase long-chain family member 4 (ACSL4), NADPH oxidase 1 (NOX1), glutathione peroxidase 4 (GPX4), and heat shock protein 27 (HSP27)], it was demonstrated that PTBP1 knockdown significantly enhances ferroptosis in endometrial cancer cells. Mechanistic studies further indicated that PTBP1 binds to the 5’ untranslated region (UTR) of solute carrier family 7 member 11 (SLC7A11) mRNA, stabilizing it and preserving SLC7A11 protein expression, thus inhibiting ferroptosis. Our study proposes a molecular mechanism by which PTBP1 promotes endometrial cancer progression by suppressing ferroptosis​​, suggesting that PTBP1 may be a promising therapeutic target for endometrial cancer.