CBX4-dependent regulation of HDAC3 nuclear translocation reduces Bmp2-induced osteoblastic differentiation and calcification in adamantinomatous craniopharyngioma

Abstract

Background Calcification of adamantinomatous craniopharyngioma (ACP) often causes problems with tumor resection, leading to a high incidence of deadly complications and tumor recurrence. Histone acetyltransferase (HAT) and histone deacetylase (HDAC) are 2 key enzymes that regulate histone acetylation and play important roles in tumor development. However, the roles of HAT and HDAC in the calcification and osteoblastic differentiation of ACP are not known. Methods In this study, primary cells were isolated from ACP tissues, and calcification was induced with bone morphogenetic protein 2 (Bmp2). HDAC3 expression was assessed in 12 tissue samples by Western blotting and immunohistochemistry. ACP calcification was assessed by Alizarin red staining. A luciferase reporter assay was performed to examine the interaction between miR-181b and the 3’-untranslated region of the polycomb chromobox 4 (CBX4) gene. Results Our results showed that the expression of HDAC3 was increased in the calcified ACP samples, but inhibition of HDAC3 promoted ACP cell calcification and osteoblastic differentiation. Mechanistically, HDAC3 nuclear translocation was suppressed by Bmp2, leading to Runx2 protein expression and Osterix, osteocalcin (OCN), osteopontin (OPN), and alkaline phosphatase (ALP) mRNA expression. In addition, this process was suppressed by CBX4, which stabilized the nuclear localization of HDAC3. miR-181b, the expression of which was increased in Bmp2-induced ACP cells, directly targeted and decreased CBX4 expression and inhibited the nuclear localization of HDAC3. Conclusions Our results demonstrate that Bmp2 increases miR-181b levels to directly target and inhibit CBX4 expression, leading to a reduction in the CBX4-dependent regulation of HDAC3 nuclear translocation, which results in Runx2 activation/osteoblastic differentiation and calcium deposition in ACP. Further studies targeting these cascades may contribute to therapeutic interventions used for recurrent ACP.

Nursing Education of Lateral Oblique Complications of Neurosurgery under Microscope

“…Yan et al said that the 2019 China Cancer Report released by the China Cancer Center indicated that about 10,000 people are diagnosed with cancer every day, an average of seven people every minute. The report pointed out that the most important treatment for cancer is surgery, so the training of surgical skills for surgeons has become particularly important [1]. Swiatek However, current methods only use two test models, which is also a limitation for most new surgeons.…”

“…Yan et al said that the 2019 China Cancer Report released by the China Cancer Center indicated that about 10,000 people are diagnosed with cancer every day, an average of seven people every minute. The report pointed out that the most important treatment for cancer is surgery, so the training of surgical skills for surgeons has become particularly important [ 1 ]. Swiatek et al said that with the rapid expansion of the enrollment of medical colleges in China, the difficulty in obtaining cadavers, the unguaranteed surgical training, the low efficiency, and high cost of the training of surgeons would greatly prolong the training cycle of a surgeon [ 2 ].…”

Involvement of MiRNA-211-5p and Arhgap11a Interaction During Osteogenic Differentiation of MC3T3-E1 Cells

“…To experimentally verify the results obtained from bioinformatics analysis, MC3T3-E1 cells were cultured with or without the osteogenic differentiation medium for 14 days. The RT-qPCR and ELISA methods were performed to determine the mRNA expressions and cellular levels of osteoblast markers, ALP, OSX, OCN, and Runx2 in the MC3T3-E1 cells (25). It was found that the mRNA expressions and cellular levels of ALP, OSX, OCN, and Runx2 were remarkably elevated in the MC3T3-E1 cells with osteoblast induction compared with undifferentiated MC3T3-E1 cells (p < 0.05, Figures 4A,B).…”

Chromobox proteins in cancer: Multifaceted functions and strategies for modulation (Review)

“…miR-129-5p (163) and miR-515-5p (164) in BC, miR-507 in GC (165), miR-6838-5p in HCC (166) and miR-497-5p in CCA (167) target CBX4 to regulate the biological characteristics of human cancers. BMP2 increases miR-181b levels to directly target and inhibit CBX4 expression in adamantinomatous craniopharyngioma (ACP), resulting in reduced regulation of CBX4-dependent HDAC3 nuclear translocation, RUNX2 activation/osteoblast differentiation and calcium deposition in ACP (168). CBX4 is upregulated in BC and shows carcinogenic activity mediated through the activation of the miR-137-mediated Notch1 signaling pathway (76).…”