KDM2A Targets PFKFB3 for Ubiquitylation to Inhibit the Proliferation and Angiogenesis of Multiple Myeloma Cells.

The lysine demethylase KDM2A (also known as JHDM1A or FBXL11) demethylates histone H3 at lysine K36 which lead to epigenetic regulation of cell proliferation and tumorigenesis. However, many biological processes are mediated by KDM2A independently by its histone demethylation activity. In the present study, we aimed to characterize the functional significance of KDM2A in multiple myeloma (MM) disease progression. Specifically, we defined that one of the key enzymes of glycolysis PFKFB3 (6-phosphofructo-2-kinase) is ubiquitylated by KDM2A which suppresses MM cell proliferation. Previous study showed that KDM2A and PFKFB3 promoted angiogenesis in various tumor cells. We further reveal that KDM2A targets PFKFB3 for ubiquitination and degradation to inhibit angiogenesis. Several angiogenic cytokines are also downregulated in MM. Clinically, MM patients with low KDM2A and high PFKFB3 levels have shown worse prognosis. These results reveal a novel function of KDM2A through ubiquitin ligase activity by targeting PFKFB3 to induce proliferation, glycolysis and angiogenesis in MM cells. The data provides a new potential mechanism and strategy for MM treatment.

Localization and potential function of androgen receptor in rat salivary gland.

AIM: To investigate the localization and quantity of androgen receptor (AR) in the salivary glands of rats with further analysis on the effect of castration. METHODS: Sixty male Wistar rats, aged 30-60 days, were randomly divided into three groups (castrated, sham-operated and normal controls) with 20 rats in each group. The rats in the castrated group were castrated and the submaxillary glands were removed after 1 week. The salivary glands of the rats in the sham-operated and the normal control groups were also removed. Parts of the salivary glands were fixed for immunohistochemistry and in situ hybridization assays. Other parts were used for Western blot. RESULTS: AR immunoreactivity in the three groups was localized in the glandular epithelial cells of the serous acinus and the glandular duct of the salivary gland, mainly in the nuclei. AR mRNA hybridization signals in the salivary glands of the castrated group were mainly distributed in the epithelial cells of the convoluted and secretary ducts; AR mRNA in the sham-operated and the normal control groups were found in the epithelial cells of the convoluted, the secretary and the excretory ducts. The quantity of AR in the salivary glands was decreased significantly in the castrated rats compared with the sham-operated and the normal controls. Moreover, epidermal growth factor (EGF) secreted by the salivary glands was also decreased in the castrated rats. CONCLUSION: Castration appears to affect the production of AR in the salivary gland and the distribution of the AR mRNA and could further affect the function of the salivary gland. The changes of AR and the distribution of AR mRNA may play an important role in the interactions between the testes and the salivary gland.

[The localization and potential function of androgen receptor mRNA in rat submaxillary].

OBJECTIVES: To study the distribution and potential function of androgen receptor (AR) mRNA and AR in rat submaxillary. METHODS: In situ hybridization using digoxigenin-labled oligonucleotide probes, cell culture and radio-immunoassay were performed to localize the AR and detect the concentration of epidermal growth factor (EGF) in culturing supernant. RESULTS: AR mRNA hybridization signals were detected in glandular epithelial cells of serous acinus and epithelial cells in all gland ducts. The signals distributed in cytoplasma of all positive cells with negative nuclei; Administration of testosterone can significantly increase the level of EGF (P < 0.05). CONCLUSIONS: The rat submaxillary not only is a target organ of androgen but also can product AR by itself. When androgen combined with androgen receptor and can submaxillary function can be infected and can result in the elevation of the level of EGF secreted.