Anti-SMC4 monoclonal antibody, clone FQS24476

Aim. To investigate the mRNA expression and clinical significance of structural maintenance of chromosomes protein 4 (SMC4) in breast cancer. Methods. A total of 23 paired samples were sequenced, and data from the Cancer Genome Atlas were analyzed. Results. SMC4 mRNA level was significantly upregulated in breast cancer tissues (P<0.001). Patients with high mRNA expression of SMC4 had significantly poor survival (P=0.012). Subgroup analyses show that in nontriple negative breast cancer (non-TNBC) patients, the high SMC4 mRNA expression, older age (>65), negative progesterone receptor, and advanced stages (III-IV) were independent risk factors (HR=3.293, 95% CI 1.257-8.625, P=0.015). In patients with TNBC, high mRNA expression of SMC4 correlated with better survival rate (P<0.046). Conclusion. SMC4 mRNA level is a good prognostic biomarker for patients with breast cancer.

Structural maintenance of chromosome (Smc) protein complex (condensin) plays a central role in organizing and compacting chromosomes, which determines DNA-binding activity and gene expression; however, the role of condensin Smc in innate immunity and inflammation remains largely unknown. Through a high-throughput screening of the epigenetic modifiers, we identified Smc4, a core subunit of condensin, to potentially promote inflammatory innate immune response. Knockdown or deficiency of Smc4 inhibited TLR- or virus-triggered production of proinflammatory cytokines IL-6, TNF-alpha and IFN-beta in macrophages. Mice with Smc4 knockdown were less susceptible to sepsis. Mechanistically, Smc4 enhanced NEMO transcription by recruiting H4K5ac to and increasing H4K5 acetylation of nemo promoter, leading to innate signals-triggered more potent activation of NF-kappa B and IRF3 pathways. Therefore, Smc4 promotes inflammatory innate immune responses by enhancing NEMO transcription, and our data add insight to epigenetic regulation of innate immunity and inflammation, and outline potential target for controlling inflammatory diseases.