Exosomal miR‐181a‐5p derived from SAOS‐2 cells promotes macrophages M2 polarization by targeting RORA

Abstract

Although the interaction between tumor cells and tumor‐associated macrophages (TAMs) has been widely studied; however, the mechanism of osteosarcoma cells in regulating the polarization of TAMs remains unclear. Exosomes from SAOS‐2 cells were isolated and validated by electron microscopy and Western blot. Transfection of indicated plasmids was applied to modify the expressions of miR‐181a‐5p and RAR‐related orphan receptor alpha (RORA). Flow cytometric analysis was carried out to analyze M1/M2 macrophage polarization. Quantitative real‐time PCR was performed to determine the levels of miR‐181a‐5p and RORA. Protein levels of CD63, CD81, RORA, CD163, CD206, IL‐10, CXCL10, and IL‐1β were evaluated by Western blot. The direct interaction of miR‐181a‐5p and RORA was validated by dual‐luciferase activity assay. The expression of miR‐181a‐5p was upregulated in osteosarcoma tissues and presented in SAOS‐2‐derived exosomes. SAOS‐2‐derived exosomes promoted the polarization of M2 macrophages by transferring miR‐181a‐5p. In addition, RORA was downregulated in osteosarcoma tissues and showed a negative correlation with miR‐181a‐5p. RORA was found to be the downstream target of miR‐181a‐5p in SAOS‐2 cells. Inhibition of RORA reversed the effects of miR‐181a‐5p knockdown on the polarization of M2 macrophages. The results showed that exosomal miR‐181a‐5p derived from osteosarcoma cells induced polarization of M2 macrophages via targeting RORA.

Tumour‐derived exosome SNHG17 induced by oestrogen contributes to ovarian cancer progression via the CCL13–CCR2–M2 macrophage axis

“…It was studied that loss of XIST could activate MSN‐c‐Met via exosomal miRNA to promote brain metastasis in breast cancer 49 . Exosomal miR‐181a‐5p derived from SAOS‐2 cells was found to promote macrophage M2 polarization by targeting RORA 50 . However, there is still little research on the function of ovarian cancer‐derived exosomes in TAM polarization and tumour development.…”

“… 49 Exosomal miR‐181a‐5p derived from SAOS‐2 cells was found to promote macrophage M2 polarization by targeting RORA. 50 However, there is still little research on the function of ovarian cancer‐derived exosomes in TAM polarization and tumour development. In this study, we discovered that exosomes from SKOV3 and ES2 cells could promote the M2 polarization of macrophages.…”

Connection between Radiation-Regulating Functions of Natural Products and miRNAs Targeting Radiomodulation and Exosome Biogenesis

“…Osteosarcoma tissues and exosomes show high levels of miR-181a-5p. Osteosarcomacell-derived exosomal miR-181a-5p enhanced macrophage M2 polarization [139], and its exosome targets PDCD6IP and PRKN were identified (Table 3). Higher stages of ovarian cancer exhibit a low level of miR-145-5p.…”