Colorectal cancer cell-secreted exosomal miRNA N-72 promotes tumor angiogenesis by targeting CLDN18.
Colorectal cancer cell-secreted exosomal miRNA N-72 promotes tumor angiogenesis by targeting CLDN18.
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发表时间：
2023
影响因子：
5.3
通讯作者：
Y. Li;Di Jiang;Zhi-Xin Zhang;Jun-Jun Zhang-Jun;Hong-Yu He;Jian-Li Liu;Ting Wang;Xia-Xia Yang-Xia
中科院分区：
文献类型：
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作者：
Y. Li;Di Jiang;Zhi-Xin Zhang;Jun-Jun Zhang-Jun;Hong-Yu He;Jian-Li Liu;Ting Wang;Xia-Xia Yang-Xia
血管生成是包括结直肠癌（CRC）在内的多种恶性肿瘤的生长和转移所必需的。CRC血管生成的分子机制尚未完全阐明。新的证据表明，分泌的microRNAs（miRNAs）可能介导肿瘤细胞和邻近内皮细胞之间的细胞间通讯，以调节肿瘤血管生成。此外，外泌体已被证明携带和递送miRNA以调节血管生成。miRNA N-72是一种新的在EGF诱导的人羊膜间充质干细胞迁移中起调节作用的miRNA。然而，miRNA N-72与癌症之间的关系仍不清楚。我们在这里发现CRC细胞可以分泌miRNA N-72。在CRC患者血清和培养的CRC细胞中检测到高水平的miRNA N-72。此外，CRC细胞分泌的miRNA N-72可以促进内皮细胞的迁移、小管形成和通透性。此外，使用小鼠异种移植模型来验证miRNA N-72对体内CRC生长、血管生成和转移的促进作用。进一步的机制分析表明，CRC细胞分泌的miRNA N-72可以通过exosomes进入内皮细胞，通过靶向CLDN 18抑制内皮细胞的细胞连接，从而促进血管生成。我们的发现揭示了CRC血管生成的新机制，并强调了分泌的miRNA N-72作为CRC治疗靶点和生物标志物的潜力。
Angiogenesis is essential for the growth and metastasis of several malignant tumors including colorectal cancer (CRC). The molecular mechanism underlying CRC angiogenesis has not been fully elucidated. Emerging evidence indicates that secreted microRNAs (miRNAs) may mediate the intercellular communication between tumor cells and neighboring endothelial cells to regulate tumor angiogenesis. In addition, exosomes have been shown to carry and deliver miRNAs to regulate angiogenesis. miRNA N-72 is a novel miRNA that plays a regulatory role in the EGF-induced migration of human amnion mesenchymal stem cells. However, the relation between miRNA N-72 and cancer remains unclear. We here found that CRC cells could secrete miRNA N-72. A high miRNA N-72 level was detected in the serum of CRC patients and the cultured CRC cells. Moreover, the CRC cell-secreted miRNA N-72 could promote the migration, tubulogenesis, and permeability of endothelial cells. In addition, the mouse xenograft model was used to verify the facilitating effects of miRNA N-72 on CRC growth, angiogenesis, and metastasis in vivo. Further mechanism analysis revealed that CRC cell-secreted miRNA N-72 could be delivered into endothelial cells via exosomes, which then inhibited cell junctions of endothelial cells by targeting CLDN18 and consequently promoted angiogenesis. Our findings reveal a novel mechanism of CRC angiogenesis and highlight the potential of secreted miRNA N-72 as a therapeutic target and a biomarker for CRC.