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<p>Non-small cell lung cancer&#xa0;(NSCLC) is recognized as one of the most aggressive cancers, and resistance to cisplatin significantly hinders effective clinical treatment. The role of the E3 ubiquitin ligase RNF180 in cisplatin resistance in NSCLC remains unclear. A549/DDP cells were transduced with lentiviral vectors to adjust RNF180 expression. In vitro experiments, nude mouse xenograft models, and bioinformatics analyses were used to verify the functions of RNF180 and its substrate, PLK2. Quantitative real-time PCR (qRT-PCR) and Western blotting were used to detect the signaling pathways. RNF180 expression was significantly lower in A549/DDP cells than in A549 cells. Overexpression of RNF180 inhibited proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and drug resistance protein expression, while promoting apoptosis in <i>vitro</i> and in <i>vivo</i>. Meanwhile, the bioinformatics database identified PLK2 as a downstream substrate of RNF180, with PLK2 overexpressed in A549/DDP cells. In <i>vitro</i> knockdown of PLK2 promoted the malignant phenotype and enhanced cisplatin resistance of A549/DDP cells. Besides, our results suggested that RNF180 inhibits NSCLC progression and attenuates cisplatin resistance by suppressing the EGFR/PI3K/AKT signaling pathway and regulating the activity of its substrate, PLK2. This study confirms that RNF180 inhibits NSCLC progression and attenuates tumor chemoresistance, and further elucidates its regulatory signaling pathways.</p>

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The E3 ubiquitin ligase RNF180 modulates the EGFR/PI3K/AKT pathway to reduce cisplatin resistance in non-small cell lung cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月10日

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  • Xiaoyan Song,
  • Wen Jiang,
  • Hongxuan Wei,
  • Yan Zhu,
  • Junmei Shu,
  • Chuandong Zhu,
  • Fangfang Chen

摘要

Non-small cell lung cancer (NSCLC) is recognized as one of the most aggressive cancers, and resistance to cisplatin significantly hinders effective clinical treatment. The role of the E3 ubiquitin ligase RNF180 in cisplatin resistance in NSCLC remains unclear. A549/DDP cells were transduced with lentiviral vectors to adjust RNF180 expression. In vitro experiments, nude mouse xenograft models, and bioinformatics analyses were used to verify the functions of RNF180 and its substrate, PLK2. Quantitative real-time PCR (qRT-PCR) and Western blotting were used to detect the signaling pathways. RNF180 expression was significantly lower in A549/DDP cells than in A549 cells. Overexpression of RNF180 inhibited proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and drug resistance protein expression, while promoting apoptosis in vitro and in vivo. Meanwhile, the bioinformatics database identified PLK2 as a downstream substrate of RNF180, with PLK2 overexpressed in A549/DDP cells. In vitro knockdown of PLK2 promoted the malignant phenotype and enhanced cisplatin resistance of A549/DDP cells. Besides, our results suggested that RNF180 inhibits NSCLC progression and attenuates cisplatin resistance by suppressing the EGFR/PI3K/AKT signaling pathway and regulating the activity of its substrate, PLK2. This study confirms that RNF180 inhibits NSCLC progression and attenuates tumor chemoresistance, and further elucidates its regulatory signaling pathways.