Constitutive activation of the NF-κB pathway is associated with diffuse large B-cell lymphoma (DLBCL) pathogenesis, but whether micro-RNA dysfunction can contribute to these events remains unclear. Starting from an integrative screening strategy, we uncovered that the negative NF-κB regulator TNFAIP3 is a direct target of miR-125a and miR-125b, which are commonly gained and/or overexpressed in DLBCL. Ectopic expression of these microRNAs in multiple cell models enhanced K63-linked ubiquitination of proximal signaling complexes and elevated NF-κB activity, leading to aberrant expression of its transcriptional targets and the development of a proproliferative and antiapoptotic phenotype in malignant B cells. Concordantly, genetic inhibition of miR-125a/miR-125b blunted NF-κB signals, whereas rescue assays and genetic modulation of a TNFAIP3-null model defined the essential role of the TNFAIP3 targeting on miR-125a/ miR-125b-mediated lymphomagenesis. Importantly, miR-125a/mir125b effects on TNFAIP3 expression and NF-κB activity were confirmed in a well-characterized cohort of primary DLBCLs. Our data delineate a unique epigenetic model for aberrant activation of the NF-κB pathway in cancer and provide a coherent mechanism for the role of these miRNAs in immune cell activation and hematopoiesis. Further, as miR-125b is a direct NF-κB transcriptional target, our results suggest the presence of a positive self-regulatory loop whereby termination of TNFAIP3 function by miR-125 could strengthen and prolong NF-κB activity.

Ba(CO) and Ba(CO) have been produced and isolated in a low-temperature neon matrix. The observed C-O stretching wavenumber for Ba(CO) of 1911.2 cm is the most red-shifted value measured for any metal carbonyl cations, indicating strong π backdonation of electron density from Ba to CO. Quantum chemical calculations indicate that Ba(CO) has a Π reference state, which correlates with the D(5d ) excited state of Ba that comprises significant Ba (5d )→CO(π* LUMO) backbonding, letting the Ba(CO) complex behave like a conventional transition-metal carbonyl. A bonding analysis shows that the π backdonation in Ba(CO) is much stronger than the Ba (5d /6s)←CO(HOMO) σ donation. The Ba cation in the D(5d ) excited state is a donor rather than an acceptor. Covalent bonding in the radical anion Ba(CO) takes place mainly through Ba(5d )←CO (π* SOMO) π donation and Ba(5d /6s)←CO (HOMO) σ donation. The most important valence functions at barium in Ba(CO) cation and Ba(CO) anion are the 5d orbitals.

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