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<p>Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related deaths worldwide, necessitating the identification of novel therapeutic targets. Mesoderm posterior bHLH transcription factor 1 (MESP1) has been implicated in various developmental processes, but its role in cancer, particularly NSCLC, is poorly understood. Given the emerging evidence linking MESP1 to cellular processes relevant to cancer biology, investigating its regulatory mechanisms in NSCLC could provide critical insights for developing new therapies.&#xa0;This study employed quantitative real-time PCR (qRT-PCR) to assess the mRNA levels of MESP1, ubiquitin specific peptidase 7 (USP7), and clusters of differentiation 163 (CD163). Western blotting was used to analyze the protein expression of MESP1 and USP7. Cellular proliferation was evaluated through colony-forming assays, while apoptosis was quantified using flow cytometry. Mitochondrial membrane potential was measured by JC-1 staining, and reactive oxygen species (ROS) levels were also analyzed via flow cytometry. Additionally, colorimetric assays were utilized to determine malondialdehyde (MDA), total iron, and Fe<sup>2+</sup> levels. The in vivo effects of MESP1 silencing on NSCLC progression were examined using a xenograft mouse model. GST-pull down assay, Co-immunoprecipitation (Co-IP) assay, and ubiquitination assay were conducted to explore the interaction between USP7 and MESP1.&#xa0;The expression of both MESP1 and USP7 was found to be upregulated in NSCLC tissues and cells when compared with normal lung tissues and normal human bronchial epithelial cells. Knockdown of MESP1 significantly inhibited NSCLC cell proliferation, induced apoptosis and promoted features associated with ferroptosis. Moreover, MESP1 silencing suppressed M2 macrophage polarization and tumor formation. Mechanistically, USP7 was identified to stabilize MESP1 protein expression through its deubiquitinating activity. Overexpression of MESP1 attenuated the inhibitory effects of USP7 silencing on NSCLC cell proliferation and M2 macrophage polarization and also mitigated the promoting effects of USP7 knockdown on apoptosis and the induction of features associated with ferroptosis.&#xa0;USP7 stabilized MESP1 to promote the malignant progression of NSCLC. The findings highlight the potential of targeting the USP7-MESP1 axis as a novel therapeutic strategy for NSCLC.</p>

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USP7 Stabilizes MESP1 To Promote the Malignant Progression of Non-Small Cell Lung Cancer

  • 期刊论文

  • 发表日期：

    2026年1月21日

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  • Shasha Jiang,
  • Liwen Rong,
  • Fei Yi,
  • Peng Yang,
  • Longjing Yang

摘要

Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related deaths worldwide, necessitating the identification of novel therapeutic targets. Mesoderm posterior bHLH transcription factor 1 (MESP1) has been implicated in various developmental processes, but its role in cancer, particularly NSCLC, is poorly understood. Given the emerging evidence linking MESP1 to cellular processes relevant to cancer biology, investigating its regulatory mechanisms in NSCLC could provide critical insights for developing new therapies. This study employed quantitative real-time PCR (qRT-PCR) to assess the mRNA levels of MESP1, ubiquitin specific peptidase 7 (USP7), and clusters of differentiation 163 (CD163). Western blotting was used to analyze the protein expression of MESP1 and USP7. Cellular proliferation was evaluated through colony-forming assays, while apoptosis was quantified using flow cytometry. Mitochondrial membrane potential was measured by JC-1 staining, and reactive oxygen species (ROS) levels were also analyzed via flow cytometry. Additionally, colorimetric assays were utilized to determine malondialdehyde (MDA), total iron, and Fe2+ levels. The in vivo effects of MESP1 silencing on NSCLC progression were examined using a xenograft mouse model. GST-pull down assay, Co-immunoprecipitation (Co-IP) assay, and ubiquitination assay were conducted to explore the interaction between USP7 and MESP1. The expression of both MESP1 and USP7 was found to be upregulated in NSCLC tissues and cells when compared with normal lung tissues and normal human bronchial epithelial cells. Knockdown of MESP1 significantly inhibited NSCLC cell proliferation, induced apoptosis and promoted features associated with ferroptosis. Moreover, MESP1 silencing suppressed M2 macrophage polarization and tumor formation. Mechanistically, USP7 was identified to stabilize MESP1 protein expression through its deubiquitinating activity. Overexpression of MESP1 attenuated the inhibitory effects of USP7 silencing on NSCLC cell proliferation and M2 macrophage polarization and also mitigated the promoting effects of USP7 knockdown on apoptosis and the induction of features associated with ferroptosis. USP7 stabilized MESP1 to promote the malignant progression of NSCLC. The findings highlight the potential of targeting the USP7-MESP1 axis as a novel therapeutic strategy for NSCLC.