Mechanism of TWEAK promoting macrophage-derived exosomal miR-7 to epithelial ovarian cancer cell through regulating Dicer / 上海交通大学学报（医学版）

ABSTRACT

Objective • To investigate the mechanism of tumor necrosis factor like weak inducer of apoptosis (TWEAK) promoting macrophagederived exosomal miR-7 to epithelial ovarian cancer (EOC). Methods • The expression of Dicer was detected by real-time PCR and Western blotting in TWEAK-stimulated macrophages. The expression of miR-7 was detected by real-time PCR in the macrophage and macrophage-derived exosome after silencing Dicer in macrophage. While in Dicer-overexpressing macrophage, real-time PCR was used to detect the expression of miR-7. Then TWEAK was used to stimulate the macrophage, and the expression of miR-7 in the macrophage and macrophage-derived exosome was detected by real-time PCR. The expression of key proteins in the nuclear factor-κB (NF-κB) pathway was detected by Western blotting in TWEAK-stimulated macrophage. After pretreatment of NF-κB inhibitor, Western blotting was used to detect the expression of Dicer and key proteins in the NF-κB pathway in TWEAKstimulated macrophage. Results • The expression of Dicer in macrophage was down-regulated after TWEAK stimulating. The expression of miR-7 was up-regulated in Dicer-silencing macrophage and macrophage-derived exosome. While the expression of miR-7 was down-regulated in the macrophage and the macrophage-derived exosome in Dicer-overexpressing macrophage after TWEAK stimulating. The expression of key proteins in the NF-κB pathway in macrophage was also up-regulated after TWEAK stimulating. After inhibition of NF-κB signaling pathway, the expression of Dicer was not significantly changed in TWEAK-stimulated macrophage compared to the control group. Conclusion • TWEAK can active NF-κB pathway and inhibit the expression of Dicer to promote macrophage-derived exosomal miR-7 to EOC cells.