Carcinoma-associated fibroblasts derived exosomes modulate breast cancer cell stemness through exonic circHIF1A by miR-580-5p in hypoxic stress

癌相关成纤维细胞衍生的外泌体在缺氧应激中通过 miR-580-5p 的外显子 circHIF1A 调节乳腺癌细胞干性

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作者:Yanxia Zhan #, Junxian Du #, Zhihui Min, Li Ma, Wei Zhang, Wei Zhu, Yonglei Liu

Abstract

Hypoxia is a common phenomenon in solid tumors. The roles of exosomes from hypoxic breast cancer stroma are less studied. So, the study was aimed to investigate the role of exosomes from hypoxic cancer-associated fibroblasts (CAFs) cells in breast cancer. The circRNA array analysis was performed to screen differential expressed circRNAs between hypoxic and normoxic CAFs exosomes. Candidate circHIF1A (circ_0032138) was screened out and it was confirmed that circHIF1A was up-regulated in the exosomes from hypoxic CAFs and their exosomes. Through investigating cellular functions including cell proliferation and stem cell features, it was demonstrated that hypoxic CAFs exosomes transferred circHIF1A into breast cancer cells, which played an important role in cancer stem cell properties sponging miR-580-5p by regulating CD44 expression. In a summary, circHIF1A from hypoxic CAFs exosomes played an important role in stem cell properties of breast cancer. CircHIF1A may act as a target molecule of breast cancer therapy.

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