Anti-MYCBP (full length) polyclonal antibody

MicroRNAs are subject to precise regulation and have key roles in tumorigenesis. In contrast to the oncogenic role of miR-22 reported in myelodysplastic syndrome (MDS) and breast cancer, here we show that miR-22 is an essential anti-tumour gatekeeper in de novo acute myeloid leukaemia (AML) where it is significantly downregulated. Forced expression of miR-22 significantly suppresses leukaemic cell viability and growth in vitro, and substantially inhibits leukaemia development and maintenance in vivo. Mechanistically, miR-22 targets multiple oncogenes, including CRTC1, FLT3 and MYCBP, and thus represses the CREB and MYC pathways. The downregulation of miR-22 in AML is caused by TET1/GFI1/EZH2/SIN3A-mediated epigenetic repression and/or DNA copy-number loss. Furthermore, nanoparticles carrying miR-22 oligos significantly inhibit leukaemia progression in vivo. Together, our study uncovers a TET1/GFI1/EZH2/SIN3A/miR-22/CREB-MYC signalling circuit and thereby provides insights into epigenetic/genetic mechanisms underlying the pathogenesis of AML, and also highlights the clinical potential of miR-22-based AML therapy.

Background: Ameloblastoma (AM) is a frequent odontogenic tumor, which is associated with high risk of recurrence. Previous studies have reported dysregulation of miRNA-516b (miR-516bis dysregulated in some malignancies); however, its biological function in AM is poorly understood. Methods: Quantitative real-time PCR was used to estimate miR-516b expression in AM tissues and cell line. CCK8, flow cytometry, wound scratch, and Transwell invasion assays were used to determine cell proliferation, cell cycle and apoptosis, migration, and invasion in AM cells, respectively. Using bioinformatics analyses and luciferase assay, a new target of miR-516b was identified, and Western blot was used to detect downstream effector proteins of miR-516b. Results: miR-516b was found to be markedly downregulated in AM tissues as compared to normal tissues. Enforced expression of miR-516b significantly inhibited cell proliferation, migration, invasion, and induced cell cycle G0/G1 phase arrest and apoptosis in AM cells. The oncogene, MYCBP, was identified as a potential miR-516b target and its depletion by siRNAs has similar effects as miR-516b overexpression on cell proliferation and mobility. However, rescued MYCBP expression partially reversed the inhibitory effects of miR-516b in AM cell lines. Further, c-myc, RECK, MMP2, and MMP9 were identified as downstream effector proteins of miR-516b. Conclusions: These results suggested that the potential suppressive role of miR-516bin AM was due to the suppression of MYCBP/c-myc/RECK/MMP pathway.