The ethylene, jasmonic acid and osmotic signaling pathways respond to environmental stimuli and in order to understand how plants adapt to biotic and abiotic stresses it is important to understand how these pathways interact each other. In this paper, we report a novel ERF protein--jasmonate and ethylene-responsive factor 3 (JERF3)--that unites these pathways. JERF3, which functions as an in vivo transcription activator in yeast, binds to the GCC box, an element responsive to ethylene/JA signaling, as well as to DRE, a dehydration-responsive element that responds to dehydration, high salt and low-temperature. Expression of JERF3 in tomato is mainly induced by ethylene, JA, cold, salt or ABA. Constitutive expression of JERF3 in transgenic tobacco significantly activated expression of pathogenesis-related genes that contained the GCC box, resulting in enhanced tolerance to salt. These results indicate that JERF3 functions as a linker in ethylene- and osmotic stress-signaling pathways.

Resistance to cancer treatment can be driven by epigenetic reprogramming of specific transcriptomes in favor of the refractory phenotypes. Here we discover that tamoxifen resistance in breast cancer is driven by a regulatory axis consisting of a master transcription factor, its cofactor, and an epigenetic regulator. The oncogenic histone methyltransferase EZH2 conferred tamoxifen resistance by silencing the expression of the estrogen receptor α (ERα) cofactor GREB1. In clinical specimens, induction of DNA methylation of a particular CpG-enriched region at the GREB1 promoter negatively correlated with GREB1 levels and cell sensitivity to endocrine agents. GREB1 also ensured proper cellular reactions to different ligands by recruiting distinct sets of ERα cofactors to cis-regulatory elements, which explains the contradictory biological effects of GREB1 on breast cancer cell growth in response to estrogen or antiestrogen. In refractory cells, EZH2-dependent repression of GREB1 triggered chromatin reallocation of ERα coregulators, converting the antiestrogen into an agonist. In clinical specimens from patients receiving adjuvant tamoxifen treatment, expression levels of EZH2 and GREB1 were correlated negatively, and taken together better predicted patient responses to endocrine therapy. Overall, our work suggests a new strategy to overcome endocrine resistance in metastatic breast cancer by targeting a particular epigenetic program.

Background: The objective of this study is to explore the association between the pretreatment systemic immune-inflammation index (SII) and prognosis in non-small cell lung cancer (NSCLC) patients.Methods: A systemic literature search of PubMed, EMBASE, the Web of Science, the Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang, VIP and SinoMed databases was performed from January 1, 1966 to April 15, 2019, to identify potential studies that assessed the prognostic role of the pretreatment SII in NSCLC. The hazard ratio (HR) and 95% confidence interval (CI) were combined to evaluate the correlation of the pretreatment SII with overall survival (OS), disease-free survival (DFS), progression-free survival (PFS) and cancer-specific survival (CSS) in NSCLC patients.Results: A total of 9 studies involving 2,441 patients were eventually included. An elevated pretreatment SII indicated significantly poorer OS (HR =1.88, 95% CI: 1.50-2.36; P<0.001) with high heterogeneity (I 2 =60.6%, P=0.019), DFS/PFS (HR =2.50, 95% CI: 1.20-5.20; P=0.014) with high heterogeneity (I 2 =58.2%, P=0.092) and CSS (HR =1.852, 95% CI: 1.185-2.915; P=0.007). Subgroup analyses further verified the above results. In addition, compared with the neutrophil to lymphocyte ratio (NLR) and the platelet to lymphocyte ratio (PLR), the SII showed a much higher prognostic value in NSCLC. Conclusions:The pretreatment SII may serve as a useful prognostic indicator in NSCLC and contribute to prognosis evaluation and treatment strategy formulation. However, more well-designed studies are warranted to verify our findings.