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.
Highlights
The tumor stroma has a higher ratio in cancer tissues such as breast cancer and influences cancer progression
To investigate the effect of Carcinoma-associated fibroblasts (CAFs) exosomal circular RNAs on the breast cancer cellular phenotypes, CAFs from breast cancer tissues were cultured in hypoxia (H-exo) and normoxia (N-exo) for 48 h, and the exosomes were taken photos under a transmission electron microscope (TEM) (Fig. 1A)
Fibroblasts can be activated to CAFs which function as a support for cancer progression including metabolism, metastasis, proliferation, anti-apoptosis, angiogenesis, and therapy resistance[3,4,5]
Summary
The tumor stroma has a higher ratio in cancer tissues such as breast cancer and influences cancer progression. Carcinoma-associated fibroblasts (CAFs) are the main cell type in tumor stroma and the emerging evidence indicates that CAFs play important roles in cancer progression[1,2]. CAFs play important roles in reprogramming the tumor microenvironment through the maintenance of the reactive stroma and participate in growth, angiogenesis, immunosuppression, metastasis, metabolism, and stemness[2,3]. CAFs communicate with other cells like cancer cells, immune cells, adipocytes through secreting various molecules or extracellular vehicles (EVs)[4]. Exosomes are 30–150 nm EVs from diverse cell secretion which exchanges the information between cells[5,6]. Exosomes act as natural vehicles delivering growth factors, chemokines, RNA, noncoding RNAs including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), circular RNA (circRNA), and other soluble mediators to recipient cells[7]
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