Scholarlink

<p>The cytochrome P450 enzyme CYP4F11, a pivotal regulator of fatty acid metabolism and drug metabolism, exhibits significantly overexpression in non-small cell lung cancer (NSCLC) and is associated with poor clinical outcomes. Through integrated analysis of TCGA/GEO datasets and immunohistochemistry validation of 235 NSCLC specimens, we established <i>CYP4F11</i> as a novel prognostic biomarker. Functional studies demonstrated that <i>CYP4F11</i> knockdown markedly impaired NSCLC cell proliferation, clonogenicity, and migration <i>in vitro</i>, moreover xenograft models confirmed its tumor-promoting role <i>in vivo</i>. Mechanistically, we identified <i>CYP4F11</i> as a direct target of tumor suppressor miR-195 via 3′-UTR binding, with miR-195-mediated suppression of <i>CYP4F11</i> leading to ubiquitin-proteasomal degradation of mitochondrial malic enzyme 2 (ME2) — a critical metabolic regulator in cancer cells. Metabolomic analyses revealed that <i>CYP4F11</i> depletion disrupts mitochondrial malate metabolism, while rescue experiments confirmed <i>ME2</i>’s pivotal role in mediating <i>CYP4F11</i>’s oncogenic effects. Our findings elucidate the <i>CYP4F11</i>/miR-195/<i>ME2</i> regulatory axis as a crucial determinant of NSCLC progression, highlighting <i>CYP4F11</i> as both a prognostic indicator and a potential therapeutic target through modulation of cancer cell metabolism.</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

CYP4F11 promotes lung cancer progression through the miR-195/ME2 pathway

  • 期刊论文

  • 发表日期：

    2025年12月8日

查看全文
  • Shan Shi,
  • Jiao Zhou,
  • Qiuyun Luo,
  • Hongtao Chen,
  • Jing Yang,
  • Liqiong Yang,
  • Lin Zhang,
  • Hongyu Zhang,
  • Dajun Yang

摘要

The cytochrome P450 enzyme CYP4F11, a pivotal regulator of fatty acid metabolism and drug metabolism, exhibits significantly overexpression in non-small cell lung cancer (NSCLC) and is associated with poor clinical outcomes. Through integrated analysis of TCGA/GEO datasets and immunohistochemistry validation of 235 NSCLC specimens, we established CYP4F11 as a novel prognostic biomarker. Functional studies demonstrated that CYP4F11 knockdown markedly impaired NSCLC cell proliferation, clonogenicity, and migration in vitro, moreover xenograft models confirmed its tumor-promoting role in vivo. Mechanistically, we identified CYP4F11 as a direct target of tumor suppressor miR-195 via 3′-UTR binding, with miR-195-mediated suppression of CYP4F11 leading to ubiquitin-proteasomal degradation of mitochondrial malic enzyme 2 (ME2) — a critical metabolic regulator in cancer cells. Metabolomic analyses revealed that CYP4F11 depletion disrupts mitochondrial malate metabolism, while rescue experiments confirmed ME2’s pivotal role in mediating CYP4F11’s oncogenic effects. Our findings elucidate the CYP4F11/miR-195/ME2 regulatory axis as a crucial determinant of NSCLC progression, highlighting CYP4F11 as both a prognostic indicator and a potential therapeutic target through modulation of cancer cell metabolism.