Exosomal lncRNA SNHG12 promotes angiogenesis and breast cancer progression

作者：Yan Chen, Yuxin Zhou, Jiafeng Chen, Jiahui Yang, Yijie Yuan, Weizhu Wu · 发表于：Breast Cancer · 年份：2024 · DOI：10.1007/s12282-024-01574-6 · 被引用次数：19 · 研究领域：Extracellular vesicles in disease、Cancer-related molecular mechanisms research、Circular RNAs in diseases

OBJECTIVE: Breast cancer is one of the most prevalent malignancies in women. Exosomes are important mediators of intercellular communication; however, their regulatory mechanisms in human umbilical vein endothelial cells (HUVECs) angiogenesis in breast cancer remain unknown. METHODS: We isolated and characterized breast cancer cell-derived exosomes and investigated their functions. Exosomal sequencing and the TCGA database were used to screen long non-coding RNA (lncRNA). In vitro and in vivo experiments were performed to investigate the role of exosomal lncRNA in HUVEC angiogenesis and tumor growth. Molecular methods were used to demonstrate the molecular mechanism of lncRNA. RESULTS: We demonstrated that breast cancer cell-derived exosomes promoted HUVEC proliferation, tube formation, and migration. Combining exosomal sequencing results with The Cancer Genome Atlas Breast Cancer database, we screened lncRNA small nucleolar RNA host gene 12 (SNHG12), which was highly expressed in breast cancer cells. SNHG12 was also upregulated in HUVECs co-cultured with exosome-overexpressed SNHG12. Moreover, overexpression of SNHG12 in exosomes increased HUVEC proliferation and migration, whereas deletion of SNHG12 in exosomes showed the opposite effects. In vivo experiments showed that SNHG12 knockdown in exosomes inhibited breast cancer tumor growth. Transcriptome sequencing identified MMP10 as the target gene of SNHG12. Functional experiments revealed that MMP10 overexpression promoted ...