KDM5B Is Essential for the Hyperactivation of PI3K/AKT Signaling in Prostate Tumorigenesis

KDM5B (lysine[K]-specific demethylase 5B) is frequently upregulated in various human cancers including prostate cancer. KDM5B controls H3K4me3/2 levels and regulates gene transcription and cell differentiation, yet the contributions of KDM5B to prostate cancer tumorigenesis remain unknown. In this study, we investigated the functional role of KDM5B in epigenetic dysregulation and prostate cancer progression in cultured cells and in mouse models of prostate epithelium–specific mutant Pten/Kdm5b. Kdm5b deficiency resulted in a significant delay in the onset of prostate cancer in Pten-null mice, whereas Kdm5b loss alone caused no morphologic abnormalities in mouse prostates. At 6 months of age, the prostate weight of Pten/Kdm5b mice was reduced by up to 70% compared with that of Pten mice. Pathologic analysis revealed Pten/Kdm5b mice displayed mild morphologic changes with hyperplasia in prostates, whereas age-matched Pten littermates developed high-grade prostatic intraepithelial neoplasia and prostate cancer. Mechanistically, KDM5B governed PI3K/AKT signaling in prostate cancer in vitro and in vivo. KDM5B directly bound the PIK3CA promoter, and KDM5B knockout resulted in a significant reduction of P110α and PIP3 levels and subsequent decrease in proliferation of human prostate cancer cells. Conversely, KDM5B overexpression resulted in increased PI3K/AKT signaling. Loss of Kdm5b abrogated the hyperactivation of AKT signaling by decreasing P110α/P85 levels in Pten/Kdm5b mice. Taken together, our findings reveal that KDM5B acts as a key regulator of PI3K/AKT signaling; they also support the concept that targeting KDM5B is a novel and effective therapeutic strategy against prostate cancer

Frontiers in zeolites: towards establishing a new discipline of condensed matter chemistry—an interview with Ruren Xu

Abstract In recent decades, the application of zeolite has been extended to many sustainable processes. Professor Ruren Xu (徐如人) of Jilin University is a leader within Chinese, Asian and worldwide zeolite communities, as well as the founder of the inorganic synthesis discipline in China and the first person in the world to propose the scientific discipline of modern inorganic synthetic chemistry. Professor Xu started his scholarly research on zeolites in the mid-1970s. He focused initially on crystallization and mechanisms of zeolite formation. In the 1980s, he gradually shifted his research to the exploration of microporous materials with novel frameworks and compositions. In 1984, he outlined new directions in the synthesis of zeolites and placed emphasis on the ‘heteroatom concept’, which turned out to be very influential and fruitful for the subsequent development of heteroatom-containing zeolite catalysts. In the following years, he and his group systematically developed new solvothermal routes for zeolite synthesis. In the late 1990s, Xu started to think about the rational synthesis of zeolites, a major challenge for zeolite as well as inorganic synthesis in general. His group developed several effective strategies for the rational design and synthesis of zeolitic materials. He is the chairman of the 15th International Zeolite Conference (15th IZC) held in 2007 for the first time in China. Because of his significant contribution to zeolite science in China, he received the National Zeolite Lifetime Achievement Award of China in 2017. NSR recently interviewed Professor Xu about the current status and future prospects of zeolites and related porous materials. This interview is dedicated to Professor Xu on his 90th birthday, in recognition of his seminal contribution to zeolite science, modern inorganic synthetic chemistry and the new discipline of condensed matter chemistry, which was first suggested by Professor Xu in 2018.</jats:p