Abstract
BackgroundIntercellular communication is crucial for breast cancer progression and metastasis. However, the role of cancer-derived exosomes and their crucial microRNA (miRNA) cargoes mediating intercellular communication requires further investigation.MethodsCancer-derived exosomes were isolated using differential centrifugation and differentially expressed miRNAs were determined by microarrays and qRT-PCR analysis. Cell proliferation, wound-healing, Transwell invasion, and tumor xenograft assays were used for functional research. Plasma exosomal RNA was isolated to verify its role as a prognostic biomarker.ResultsWe found that the tumor-promoting capacity of the exosomes was positively related to their cells of origin. MiR-7641 was identified to be the most differentially expressed miRNA, both at endogenous and secretory levels in high-metastatic cancer cells. MiR-7641 could promote tumor cell progression and metastasis, and that these functions of miR-7641 could alter recipient cells via transportation of exosomes. Additionally, exosomal miR-7641 could promote tumor growth in vivo; and its levels were significantly elevated in the plasma of patients with distant metastasis. Bioinformatics analysis has suggested that miR-7641 is correlated with breast cancer survival, and several important cellular and biological processes are closely targeted by miR-7641.ConclusionThe findings indicate miR-7641 to be an important component of the cancer exosomes in promoting tumor progression and metastasis via intercellular communication. Additionally, exosomal miR-7641 may serve as a promising non-invasive diagnostic biomarker and potential targetable candidate in breast cancer treatment.BWySRQX9DMANyj4v-XQwBNVideo
Highlights
Intercellular communication is crucial for breast cancer progression and metastasis
Isolation and characterization of exosomes released from tumor cells Exosomes in conditioned media were isolated using differential centrifugation from three breast cancer cell lines (MCF-7, HCC-1937, and MDA-MB-231)
We identified that miR-7641 could promote breast cancer cell proliferation and invasion, and that its ability to cause epigenetic modulation could affect recipient cells after transportation via exosomes
Summary
Intercellular communication is crucial for breast cancer progression and metastasis. The role of cancer-derived exosomes and their crucial microRNA (miRNA) cargoes mediating intercellular communication requires further investigation. The physiological purpose for cancer cells to secrete exosomes remains largely unknown and needs investigation; recent studies indicate a functional and selective accumulation of cellular bioactive components in the exosomes, suggesting their involvement in cellto-cell communication during tumor progression and. Several studies showed that exosomes released from highly metastatic cancer cells could be taken up by other cells, and transfer metastatic capability to non-metastatic cells[8, 9]. There is considerable evidence indicating that miRNAs are involved in the progression and metastasis of cancer cells via epigenetic regulations[12]. Which are the key miRNAs transferred as cargoes via cancer-derived exosomes in promoting tumor proliferation and metastasis remains unclear
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