Jiangsu Key Laboratory of Oral Disease, & Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing Medical University, Nanjing 210029, China.
Department of Oral and Maxillofacial Surgery, The Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing 210029, China.
Carcinogenesis. 2022 Aug 30;43(7):682-692. doi: 10.1093/carcin/bgac033.
MicroRNA (miR)-23b-3p is known to target various genes that are involved in cancer-related pathways. Exosomes are emerging intercellular communication agents. Exosomes secreted by cancer cells can deliver active molecules to the surrounding stromal cells, thereby influencing the recipient cells and promoting the development of cancers. However, the role of exosomal miR-23b-3p in salivary adenoid cystic carcinoma (SACC) is not yet clear. In this study, we set out to investigate the potential role of cancer-derived exosomal miR-23b-3p-related phosphatase and tensin homolog deleted on chromosome 10 in the alteration of angiogenesis and vascular permeability in SACC. We investigated the effect of exosomal miR-23b-3p on the progression of SACC. In vitro experiments indicated that exosomal miR-23b-3p led to an upregulation of vascular permeability, and reduced expression of tight junction proteins. In addition, exosomal miR-23b-3p also enhanced angiogenesis and migration. Next, the angiogenic effect of exosomal miR-23b-3p was validated in vivo, as it led to an increase in the tumor microvasculature. Furthermore, the growth rate of SACC was faster after injection of exosomes loaded with cholesterol-modified miR-23b-3p in mice. In conclusion, these results revealed that SACC cell-derived exosomes play an important role in promoting angiogenesis and local vascular microleakage of SACC by transporting miR-23b-3p, which suggests that miR-23b-3p in the exosomes may be a potential biomarker for distant metastasis of SACC. This suggests the potential of a novel therapeutic target by delivering anti-miR-23b-3p that focuses on exosomes.
微小 RNA（miR）-23b-3p 已知可靶向参与癌症相关途径的各种基因。外泌体是新兴的细胞间通讯剂。癌细胞分泌的外泌体可以将活性分子递送到周围的基质细胞，从而影响受体细胞并促进癌症的发展。然而，外泌体 miR-23b-3p 在唾液腺腺样囊性癌（SACC）中的作用尚不清楚。在这项研究中，我们旨在研究源自癌症的外泌体 miR-23b-3p 相关磷酸酶和张力蛋白同源物缺失 10 号染色体（PTEN）在 SACC 中改变血管生成和血管通透性的潜在作用。我们研究了外泌体 miR-23b-3p 对 SACC 进展的影响。体外实验表明，外泌体 miR-23b-3p 导致血管通透性上调，并降低紧密连接蛋白的表达。此外，外泌体 miR-23b-3p 还增强了血管生成和迁移。接下来，在体内验证了外泌体 miR-23b-3p 的血管生成作用，因为它导致肿瘤微血管增加。此外，在小鼠中注射载有胆固醇修饰的 miR-23b-3p 的外泌体后，SACC 的生长速度更快。总之，这些结果表明，SACC 细胞来源的外泌体通过转运 miR-23b-3p 在促进 SACC 的血管生成和局部血管微渗漏方面发挥重要作用，这表明外泌体中的 miR-23b-3p 可能是 SACC 远处转移的潜在生物标志物。这表明通过递送针对外泌体的抗 miR-23b-3p 来提供新的治疗靶标具有潜力。
