BackgroundEpithelial-mesenchymal transition (EMT) is a crucial step for solid tumor progression and plays an important role in cancer invasion and metastasis. RNF8 is an ubiquitin E3 ligase with RING domain, and plays essential roles in DNA damage response and cell cycle regulation. However the role of RNF8 in the pathogenesis of breast cancer is still unclear.MethodsThe expression of RNF8 was examined in different types of breast cell lines by Western Blotting. EMT associated markers were examined by Immunofluorescence and Western Blotting in MCF-7 when RNF8 was ectopically overexpressed, or in MDA-MB-231 when RNF8 was depleted. Transwell and wound healing assays were performed to assess the effect of RNF8 on cell mobility. The xenograft model was done with nude mice to investigate the role of RNF8 in tumor metastasis in vivo. Breast tissue arrays were used to examine the expression of RNF8 by immunohistochemistry. Kaplan-Meier survival analysis for the relationship between survival time and RNF8 signature in breast cancer was done with an online tool (http://kmplot.com/analysis/).ResultsRNF8 is overexpressed in highly metastatic breast cancer cell lines. Overexpression of RNF8 in MCF-7 significantly promoted EMT phenotypes and facilitated cell migration. On the contrary, silencing of RNF8 in MDA-MB-231 induced MET phenotypes and inhibited cell migration. Furthermore, we proved that these metastatic behavior promoting effects of RNF8 in breast cancer was associated with the inactivation of GSK-3β and activation of β-catenin signaling. With nude mice xenograft model, we found that shRNA mediated-downregulation of RNF8 reduced tumor metastasis in vivo. In addition, we found that RNF8 expression was higher in malignant breast cancer than that of the paired normal breast tissues, and was positively correlated with lymph node metastases and poor survival time.ConclusionsRNF8 induces EMT in the breast cancer cells and promotes breast cancer metastasis, suggesting that RNF8 could be used as a potential therapeutic target for the prevention and treatment of breast cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-016-0363-6) contains supplementary material, which is available to authorized users.

The meson static properties are investigated in Pauli-Villars regularized Nambu-Jona-Lasinio model in strong magnetic field. The quark dimension reduction leads to not only the magnetic catalysis effect on chiral symmetry restoration but also a sudden jump of the mass of the Goldstone mode at the Mott transition temperature.PACS numbers: 75.30.Kz, 11.30.Qc, 21.65.Qr It is well known that, the quark dimension reduction in magnetic field leads to an increasing critical temperature of chiral restoration, namely the magnetic catalysis effect [1][2][3][4][5][6][7]. From the Goldstone theorem, the spontaneous breaking of a global symmetry implies the existence of Goldstone bosons. In two-flavor case, the neutral pion is identified as the Goldstone mode in the presence of a magnetic field. The pion properties such as its mass and decay constant play an important role in chiral dynamics [8,9]. For instance, the neutral mesons are potential for explaining the inverse magnetic catalysis [10,11] and delayed magnetic catalysis [12].The Nambu-Jona-Lasinio (NJL) model at quark level describes well the chiral symmetry breaking in vacuum and its restoration at finite temperature and baryon density [13][14][15][16][17]. In the model, mesons are treated as quantum fluctuations, and neutral mesons can be affected by the external magnetic field through their constituent quarks. The neutral mesons in magnetized NJL model are investigated in vacuum and at finite temperature by taking different methods like the assumption of four-momentum independent meson polarizations [14], magnetic field independent regularization scheme [18,19], and derivative expansion [20,21] and Φ-derivable approach [22]. In this paper, we focus on how the quark dimension reduction in magnetic field affects the neutral meson properties at finite temperature and density in the Pauli-Villars regularization scheme.The SU(2) NJL model is defined through the Lagrangian density [13][14][15][16][17] (1) where the covariant derivative D µ = ∂ µ − iQA µ couples quarks to the external magnetic field B = (0, 0, B) in z-direction, Q = diag(Q u , Q d ) = diag(2e/3, −e/3) and µ = diag(µ u , µ d ) = diag(µ B /3, µ B /3) are electric charge and quark chemical potential matrices in flavor space with µ B being baryon chemical potential, G is the coupling constant in scalar and pseudo-scalar channels, and m 0 is the current quark mass characterizing the explicit chiral symmetry breaking.Taking the Leung-Ritus-Wang method [23][24][25][26][27], the quark condensate ψ ψ or the dynamical quark mass m q = m 0 − G ψ ψ at mean field level is controlled by the gap equationwith J 1 = N c f,n α n |Q f B|/(2π) dp z /(2π)J 0 /(2E f ) and, where N c = 3 is the number of colors which is trivial in the NJL model, α n = 2 − δ n0 is the spin degeneracy, and E ± f = E f ± µ B /3 are the quark energies with E f = p 2 z + 2n|Q f B| + m 2 q . Note that, the quark three-momentum integration in vacuum is reduced to a summation over Landau energy levels plus a onedimensional momentum integration in ...

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We consider the two-loop corrections to the HW+W− vertex at order ααs. We construct a canonical basis for the two-loop integrals using the Baikov representation and the intersection theory. By solving the ϵ-form differential equations, we obtain fully analytic expressions for the master integrals in terms of multiple polylogarithms, which allow fast and accurate numeric evaluation for arbitrary configurations of external momenta. We apply our analytic results to the decay process H → νeeW, and study both the integrated and differential decay rates. Our results can also be applied to the Higgs production process via W boson fusion.