Increasing evidence indicates that various cancer cell types are capable of producing IgG. The exact function of cancer-derived IgG has, however, not been elucidated. Here we demonstrated the expression of IgG genes with V(D)J recombination in 80 cases of colorectal cancers, 4 colon cancer cell lines and a tumor bearing immune deficient mouse model. IgG expression was associated with tumor differentiation, pTNM stage, lymph node involvement and inflammatory infiltration and positively correlated with the expressions of Cyclin D1, NF-κB and PCNA. Furthermore, we investigated the effect of cancer-derived IgG on the malignant behaviors of colorectal cancer cells and showed that blockage of IgG resulted in increased apoptosis and negatively affected the potential for anchor-independent colony formation and cancer cell invasion. These findings suggest that IgG synthesized by colorectal cancer cells is involved in the development and growth of colorectal cancer and blockage of IgG may be a potential therapy in treating this cancer.

Density functional theory (DFT) calculations were used to study the mechanism for the cleavage reaction of the RNA analogue HpPNP (HpPNP = 2-hydroxypropyl-4-nitrophenyl phosphate) catalyzed by the dinuclear Zn(II) complex of 1,3-bis(1,4,7-triazacyclonon-1-yl)-2-hydroxypropane (Zn(2)(L(2)O)). We present a binding mode in which each terminal phosphoryl oxygen atom binds to one zinc center, respectively, and the nucleophilic 2-hydroxypropyl group coordinates to one of the zinc ions, while the hydroxide from deprotonation of a water molecule coordinates to the other zinc ion. Our calculations found a concerted mechanism for the HpPNP cleavage with a 16.5 kcal/mol reaction barrier. An alternative proposed stepwise mechanism through a pentavalent oxyphosphorane dianion reaction intermediate for the HpPNP cleavage was found to be less feasible with a significantly higher energy barrier. In this stepwise mechanism, the deprotonation of the nucleophilic 2-hydroxypropyl group is accompanied with nucleophilic attack in the rate-determining step. Calculations of the nucleophile (18)O kinetic isotope effect (KIE) and leaving (18)O KIE for the concerted mechanism are in reasonably good agreement with the experimental values. Our results indicate a specific-base catalysis mechanism takes place in which the deprotonation of the nucleophilic 2-hydroxypropyl group occurs in a pre-equilibrium step followed by a nucleophilic attack on the phosphorus center. Detailed comparison of the geometric and electronic structure for the HpPNP cleavage reaction mechanisms in the presence/absence of catalyst revealed that the catalyst significantly altered the determining-step transition state to become far more associative or tight, that is, bond formation to the nucleophile was remarkably more advanced than leaving group bond fission in the catalyzed mechanism. Our results are consistent with and provide a reliable interpretation for the experimental observations that suggest the reaction occurs by a concerted mechanism (see Humphry, T.; Iyer, S.; Iranzo, O.; Morrow, J. R.; Richard, J. P.; Paneth, P.; Hengge, A. C. J. Am. Chem. Soc. 2008, 130, 17858-17866) and has a specific-base catalysis character (see Yang, M.-Y.; Iranzo, O.; Richard, J. P.; Morrow, J. R. J. Am. Chem. Soc. 2005, 127, 1064-1065).

A recent success in which the engineered iron-haem enzymes P411CHA′ aminate the intermolecular benzylic C–H bond with both high efficiency and stereoselectivity solves a long-standing challenge in synthetic chemistry (Nat. Chem.20179629634). The mechanism, reactivity, and stereoselectivity of this reaction were studied by quantum mechanical (QM)/molecular mechanical (MM) calculations in this work. To understand better the origin of such an excellent catalytic performance of biocatalyst P411CHA′, iron-cofactor FePIX alone for the intermolecular C–H bond amination was also theoretically investigated as a comparison. The catalytic cycle includes two processes: N2 dissociation and nitrene transfer. The calculation results show that P411CHA′ enzyme can catalyze intermolecular C–H amination with high reactivity and stereoselectivity, whereas the FePIX-catalyzed reaction has much higher barriers for both N2 dissociation and nitrene transfer compared to P411CHA′. The reason for this dramatic difference in catalytic reactivity between P411CHA′ and FePIX is that the former but not the latter allows the formation of precursors B- 5 PR1 and B- 3 PR2, which are structurally close to transition states B- 3 TS1 and B- 3 TS2 and accelerate N2 dissociation and nitrene transfer, respectively. The mutated residues (A82L A78V F263L) assist the formations of B- 5 PR1 and B- 3 PR2 via reducing effectively the size of the haem distal pocket. High stereoselectivity of P411CHA′ stems from the steric effect in H-abstraction. A theoretical analysis on how para substituent R affects reactivity was also carried out. A strong π-type electron-donating group on the substrate enhances significantly the reactivity of P411CHA′-catalyzed intermolecular C–H amination. These results provide valuable information for designing and constructing environmentally friendly biocatalytic C–H amination systems with high reactivity and stereoselectivity.

MicroRNAs (miRNAs) are small noncoding RNAs, which downregulate gene expression by repressing or degrading mRNA targets. Lung cancer (LC), together with liver and colorectal cancers are the three leading causes of cancer death worldwide, and 80% of LCs belong to non-small cell lung cancers (NSCLCs). Despite a great advancement in developing distinct and delicate tools for early diagnosis and targeted therapies over the last decade, only about 15% of the NSCLC patients eventually survived. MiRNAs are frequently dysregulated in carcinoma, including LC. Numerous lines of evidence have demonstrated various roles played by miRNAs in the development and progression of LC. In this review, we propose to summarize the current understanding of miRNAs in LC, with a particular focus on translational application of miRNAs as novel diagnostic and prognostic biomarkers and tools for treatment.