MicroRNA-506 inhibits the proliferation and invasion of mantle cell lymphoma cells by targeting B7-H3

Background: Aberrant expression of B7 homologue 3 (B7-H3) has been observed in various malignancies. Our previous study demonstrated that knocking down of B7-H3 inhibited cell proliferation, invasion and enhanced the therapeutic efficacy of chemotherapy in mantle cell lymphoma (MCL). However, the mechanism regulating of B7-H3 expression remains unknown. Here, we present a new regulatory microRNA of B7-H3, miR-506, that directly targets B7-H3 and may play an inhibitory role in MCL progression. Methods: The expression of miR-506 and B7-H3 was investigated by real-time quantitative PCR (RTqPCR). B7-H3 was confirmed to be a novel direct target gene of miR-506 by a dual-luciferase assay and western blot analysis. MiR-506 overexpression in the Mayer and Z138 MCL cell lines was established using lentiviral transduction. Cell counting kit-8, flow cytometry and Transwell assays were used to detect changes in cell proliferation, cycle distribution, migration and invasion, respectively. Results: The RT-qPCR results showed that miR-506 was expressed at a low level, while B7-H3 was overexpressed in MCL patients and cell lines. By using a bioinformatics analysis combined with a dual luciferase assay, we determined that miR-506 could target the 3'-untranslated region (3'-UTR) of B7-H3 mRNA. Moreover, miR-506 had a negative regulatory effect on B7-H3 expression according to the western blotting and RT-qPCR results. In terms of function, increased expression of miR-506 led to reduced MCL cell proliferation, invasion and migration, caused cell cycle arrested at GO/G1 phase, similar to the effects of B7-H3 knockdown. Furthermore, we measured the expression of invasion-related proteins by western blotting and found that miR-506 could reduce MMP-2 and MMP-9 expression in MCL cells. Rescue experiments suggested that the restoration of B7-H3 expression in MCL cells reversed the inhibition of proliferation and invasion induced by miRNA-506 overexpression. Conclusions: Our findings suggest that miR-506 functions as a tumor suppressor miRNA and plays a significant role in inhibiting human MCL cell proliferation and metastasis by suppressing B7-H3 expression. (C) 2018 Elsevier Inc. All rights reserved.