Scholarlink

<p>Currently, there are no effective prevention or therapeutic methods for breast cancer bone metastasis (BC-BM), which leading to severe skeletal complications and increased mortality. Understanding the mechanisms underlying BC-BM could provide potential strategies for its prevention and treatment. In this study, we identified a new microprotein encoded by lncRNA LINC00263, which we named LINC00263-encoded protein (LINC00263-P), was significantly upregulated in bone metastatic breast cancer tissues and correlated with BC-BM. Overexpression of LINC00263 significantly promoted BC-BM, while treatment with the neutralizing anti-LINC00263-P antibody effectively inhibited BC-BM. Mechanically, the LINC00263-P binds to integrin αvβ3 for activating Src/Syk/Vav-3 axis and yes-associated protein 1 (YAP1) pathway, which enhanced osteoclastogenesis and diminishes ferroptosis in osteoclasts, thereby creating an osteolytic bone metastasis niche that fosters BC-BM. Importantly, treatment with angoroside C, an active component from the traditional Chinese medicine Scrophulariae Radix extract, effectively blocked the binding of LINC00263-P to αvβ3, thereby inhibiting abnormal osteoclastogenesis and preventing BC-BM. These findings highlight the crucial role of microprotein LINC00263-P in disrupting bone homeostasis and propose a potential molecular mechanism of BC-BM.</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

A microprotein encoded by LINC00263 promotes breast cancer osteolytic bone metastasis by inducing osteoclastogenesis and inhibiting osteoclast ferroptosis

  • 期刊论文

  • 发表日期：

    2025年4月12日

查看全文
  • Suwen Chen,
  • Miaoling Tang,
  • Xuexin Yu,
  • Wanying Qian,
  • Yingru Xu,
  • Jun Li,
  • Geyan Wu,
  • Shuxia Zhang

摘要

Currently, there are no effective prevention or therapeutic methods for breast cancer bone metastasis (BC-BM), which leading to severe skeletal complications and increased mortality. Understanding the mechanisms underlying BC-BM could provide potential strategies for its prevention and treatment. In this study, we identified a new microprotein encoded by lncRNA LINC00263, which we named LINC00263-encoded protein (LINC00263-P), was significantly upregulated in bone metastatic breast cancer tissues and correlated with BC-BM. Overexpression of LINC00263 significantly promoted BC-BM, while treatment with the neutralizing anti-LINC00263-P antibody effectively inhibited BC-BM. Mechanically, the LINC00263-P binds to integrin αvβ3 for activating Src/Syk/Vav-3 axis and yes-associated protein 1 (YAP1) pathway, which enhanced osteoclastogenesis and diminishes ferroptosis in osteoclasts, thereby creating an osteolytic bone metastasis niche that fosters BC-BM. Importantly, treatment with angoroside C, an active component from the traditional Chinese medicine Scrophulariae Radix extract, effectively blocked the binding of LINC00263-P to αvβ3, thereby inhibiting abnormal osteoclastogenesis and preventing BC-BM. These findings highlight the crucial role of microprotein LINC00263-P in disrupting bone homeostasis and propose a potential molecular mechanism of BC-BM.