Emerging evidence suggests that USP39 plays an important role in the development of hepatocellular carcinoma (HCC). However, the molecular mechanism by which USP39 promotes HCC progression has not been well defined, especially regarding its putative ubiquitination function. Zinc-finger E-box-binding homeobox 1 (ZEB1) is a crucial inducer of epithelial-to-mesenchymal transition (EMT) to promote tumor proliferation and metastasis, but the regulatory mechanism of ZEB1 stability in HCC remains enigmatic. Here, we reveal that USP39 is highly expressed in human HCC tissues and correlated with poor prognosis. Moreover, USP39 depletion inhibits HCC cell proliferation and metastasis by promoting ZEB1 degradation. Intriguingly, deubiquitinase USP39 has a direct interaction with the E3 ligase TRIM26 identified by co-immunoprecipitation assays and immunofluorescence staining assays. We further demonstrate that TRIM26 is lowly expressed in human HCC tissues and inhibits HCC cell proliferation and migration. TRIM26 promotes the degradation of ZEB1 protein by ubiquitination in HCC. Deubiquitinase USP39 and E3 ligase TRIM26 function in an antagonistic pattern, but not a competitive pattern, and play key roles in controlling ZEB1 stability to determine the HCC progression. In summary, our data reveal a previously unknown mechanism that USP39 and TRIM26 balance the level of ZEB1 ubiquitination and thereby determine HCC cell proliferation and migration. This novel mechanism may provide new approaches to target treatment for inhibiting HCC development by restoring TRIM26 or suppressing USP39 expression in HCC cases with high ZEB1 protein levels.

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Corilagin, a unique component of the tannin family, has been identified in several medicinal plants. In previous literature, corilagin exhibited a marked anticancer property in a variety of human cancer cells. However, the biological effects of corilagin on gastric cancer and the mechanisms involved remain to be fully elucidated. In the present study, it was reported that corilagin induced inhibition of cell growth in SGC7901 and BGC823 cells in a concentration-dependent manner. It was found that corilagin exhibited less toxicity towards normal GES-1 cells. Furthermore, the study showed that corilagin induced the apoptosis of gastric cancer cells mainly via activating caspase-8, -9, -3 and poly ADP-ribose polymerase proteins. Simultaneously, it was verified that corilagin triggered autophagy in gastric cancer cells and the inhibition of autophagy improved the activity of corilagin on cell growth suppression. In addition, corilagin significantly increased intracellular reactive oxygen species production, which is important in inhibiting the growth of gastric cancer cells. Finally, it was shown that necroptosis cannot be induced by corilagin-incubation in SGC7901 and BGC823 cell lines. Consequently, these findings indicate that corilagin may be developed as a potential therapeutic drug for gastric cancer.

A new non-classical theory of elastic dielectrics is developed using the couple stress and electric field gradient theories that incorporates the couple stress, quadrupole and curvature-based flexoelectric effects. The couple stress theory and an extended Gauss’s law for elastic dielectrics with quadrupole polarization are applied to derive the constitutive relations of this new theory through energy conservation. The governing equations and the complete boundary conditions are simultaneously obtained through a variational formulation based on the Gibbs-type variational principle. The constitutive relations of general anisotropic and isotropic materials with the corresponding independent material constants are also provided, respectively. To illustrate the newly proposed theory and to show the flexoelectric effect in isotropic materials, one pure bending problem of a simply supported beam is analytically solved by directly applying the formulas derived. The analytical results reveal that the flexoelectric effect is present in isotropic materials. In addition, the incorporation of both the couple stress and flexoelectric effects always leads to increased values of the beam bending stiffness.