The mechanism of exosome delivered circ-PDE7B promoting liver metastasis of breast cancer.

Abstract

e13016 Background: According to “seed and soil” hypothesis, tumor microenvironments have major effects on the survival and metastasis of cancers, including breast cancer. Importantly, exosomes are believed to partake in cellular communications through delivering oncogenic ncRNAs (including circRNAs) to the recipient cells and tumor microenvironment, which resulting in distant metastasis. Unfortunately, exosomes delivering circRNAs from breast cancer cells still remained many potential functions that are not completely understood in the progression of liver metastasis of breast cancer. This study aims to provide a theoretical basis to use stable exosomal circRNAs as new biomarkers and target spot for the liver metastasis of breast cancer. Methods: A strategy combining RNA-sequencing technique, RT-qPCR and bioinformatic analysis were used to determine the level of differential expressed circRNAs in tissue exosomes (n=5) and serum exosomes samples (n=5) from liver metastatic breast cancer patients compared with healthy person. The expression of circPDE7B was also detected in tumor tissues (n=10) from liver metastatic patients compared with healthy person, breast cancer cell lines (MDA-MB-231), high-liver metastatic cell lines (LM-MDA-MB-231), exosome from MDA-MB-231 (231/exo) and from LM-MDA-MB-231 (LM-231/exo) by RT-qPCR. In animal experiments, exosomes (enriched in circPDE7B) were injected from tail vein for 24h, follow up with injection with LM-MDA-MB-231 cells, then, fluorescence imaging and pathology showed the metastasis in liver. Results: Isolated serum exosomes were characterization by transmission electron microscope (TEM) and Nanosight 300 (NTA 300) system. We profiled the circRNAs in the tissue and serum exosomes samples from liver metastatic patients and healthy person by RNA sequencing and detected 332 significantly differentially-expressed circRNAs. After bioinformatic analysis with GEO database, circPDE7B was chose to further study. RT-qPCR results showed that higher expression of circPDE7B in liver metastatic tissue and LM-MDA-MB-231, also in LM-231/exo. Moreover, overexpressed circPDE7B in exosomes from breast cancer changes premetastatic microenvironment of the liver microenvironment, which can promote the occurrence of breast cancer liver metastasis. Conclusions: The expression of circPDE7B was found significantly upregulated in tissue and serum exosomes from liver metastatic breast cancer patients. Moreover, circPDE7B could promote liver metastasis of breast cancer. Therefore, this study provides a fresh perspective on novel therapeutic targets and potential biomarkers for liver metastasis from exosomal circRNAs.