Rabbit Anti-Human EZH2 monoclonal antibody, clone KK190-0

Current reports refer to the role of long noncoding RNA (lncRNA) prostate androgen-regulated transcript 1 (PART1) as a tumor suppressor in some types of cancer but as an oncogene in other kinds of cancer. In gastric cancer, it had been reported to be downregulated. However, the clinical significance and underlying mechanism of PART1 function in gastric cancer remains undefined. Here, seven differential expression levels of noncoding RNAs (DE-lncRNAs) were screened from gastric cancer through a probe reannotation of a human exon array. PART1 was selected for further study because of its high fold change number. In our cohort, PART1 was identified as a significant downregulated lncRNA in gastric cancer tissues by qPCR and in situ hybridization (ISH), and its low expression was significantly correlated with postoperative metastasis and short overall survival time after surgery. Through the results of gain-of-function experiments, PART1 was confirmed as a tumor suppressor that can decrease not only cell viability, migration, and invasion in vitro but also tumorigenesis and tumor metastasis in vivo. Mechanistically, RNA pull-down and RNA-binding protein immunoprecipitation (RIP) showed that PART1 interacts with androgen receptor (AR), and then, promyelocytic leukemia zinc finger (PLZF) is upregulated in an androgen-independent manner. In a chain reaction, chromatin immunoprecipitation (ChIP) assay additionally illustrated that PLZF upregulation increased the enrichment of EZH2 and H3K27 trimethylation in the platelet-derived growth factor (PDGFB) promotor, thereby inhibition of PDGFB and the subsequent PDGFR beta/PI3K/Akt signaling pathway. Based on these findings, we showed PART1 plays a tumor suppressor rolebypromoting PLZF expression followed by recruitment of EZH2 to mediate epigenetic PDGFB silencing and downstream PI3K/Akt inhibition, suggesting that PART1 has a key role in restraining the aggressive ability of GC cells and providing a novel perspective on lncRNAs in GC progression.

Epigenetic modifications to histones dictate the differentiation of naive CD4(+) T cells into different subsets of effector T helper (T-H) cells. The histone methyltransferase enhancer of zeste homolog 2 (EZH2) has been implicated in the mechanism regulating the differentiation of T(H)1, T(H)2 and regulatory T (T-reg) cells. However, whether and how EZH2 regulates follicular helper T (T-FH) cell differentiation remain unknown. Using a mouse model of acute lymphocytic choriomeningitis virus (LCMV) infection, we observed abundant EZH2 expression and associated H3K27me3 modifications preferentially in the early committed virus-specific T-FH cells compared to those in T(H)1 cells. Ablation of EZH2 in LCMV-specific CD4(+) T cells leads to a selective impairment of early T-FH cell fate commitment, but not late T-FH differentiation or memory T-FH maintenance. Mechanistically, EZH2 specifically stabilizes the chromatin accessibility of a cluster of genes that are important for T-FH fate commitment, particularly B cell lymphoma 6 (Bcl6), and thus directs T-FH cell commitment. Therefore, we identified the chromatin-modifying enzyme EZH2 as a novel regulator of early T-FH differentiation during acute viral infection.