Inhibition of UBA52 induces autophagy via EMC6 to suppress hepatocellular carcinoma tumorigenesis and progression.

Ubiquitin A-52 residue ribosomal protein fusion product 1 (UBA52) has a role in the occurrence and development of tumours. However, the mechanism by which UBA52 regulates hepatocellular carcinoma (HCC) tumorigenesis and progression remains poorly understood. By using the Cell Counting Kit (CCK-8), colony formation, wound healing and Transwell assays, we assessed the effects of UBA52 knockdown and overexpression on the proliferation and migration of HCC cells in vitro. By establishing subcutaneous and metastatic tumour models in nude mice, we evaluated the effects of UBA52 on HCC cell proliferation and migration in vivo. Through bioinformatic analysis of data from the Gene Expression Profiling Interactive Analysis (GEPIA) and The Cancer Genome Atlas (TCGA) databases, we discovered that UBA52 is associated with autophagy. In addition, we discovered that HCC tissues with high UBA52 expression had a poor prognosis in patients. Moreover, knockdown of UBA52 reduced HCC cell growth and metastasis both in vitro and in vivo. Mechanistically, knockdown of UBA52 induced autophagy through EMC6 in HCC cells. These findings suggest that UBA52 promoted the proliferation and migration of HCC cells through autophagy regulation via EMC6 and imply that UBA52 may be a viable novel treatment target for HCC patients.

Topology Effects of Poly(2-ethyl-2-oxazoline) Brushes with Various Architectures for Antifouling Behavior under Shear Flow.

Polymer brushes with different topological architectures exhibit unparalleled interfacial and physicochemical properties and are being widely utilized in antifouling applications. However, there is an absence of a thorough understanding of the antifouling process of dynamic flow mediated by the topological structure of polymer brushes. Here, it is highlighted how the interface parameters related to biofouling in flowing carrier fluid are tuned by topologically different architectures. The mechanism by which three brushes with various topological structures (cyclic, looped, and linear brushes) encounter biological media was revealed by relating protein adhesion with nanomechanics and protein conformational transitions on poly(2-ethyl-2-oxazoline) (PEtOx) brushes. In contrast to the classically linear analogue, the cyclic PEtOx brushes confered an enhanced steric barrier and excellent lubrication at the critical density region. The impenetrable and smoother layer prevented the approach and shortened the residence time for protein on the surface, providing optimal antifouling properties at low shear rates. The looped brushes also significantly inhibited protein adhesion under prolonged high shear rates due to their unshakable conformational characteristics. These findings detailed a new evaluation framework behind polymer brushes of topology-driven biofouling repulsion under flow conditions and pointed the way toward a promising approach for the effectiveness of biomaterial design.

Volume Overlap Variation within Hyperbranched Polymer Brushes Resolves Topology Effects against Protein Fouling.

Hyperbranched polymer brushes with a three-dimensional dendritic structure are used in antifouling applications to obtain bioinert and compact dendritic structures. Though hyperbranched polyglycerol (HPG) is extensively utilized in the antifouling layer, there is still a lack of direct studies on the relationship between the interfacial properties and topology effect of hyperbranched polymer brushes. Here, we established the degree of chain volume overlap (Dv) to characterize the spatial shielding efficiency generated by HPG brushes and investigated the impact mechanism of the variable chain length on the interfacial physicochemical properties. The results revealed the Dv-relevant feature of performance that the most densely packed HPG brushes for a medium-length LHPG3.07 enable the functional surface to display optimal antifouling performance toward protein adsorption by forming the most effective space barrier and hydrated layer in appropriate molecular weights and graft density. Moreover, we clarified the advance of hyperbranched polymer brushes exhibited in topology effects for imparting surface-enhanced resistance to biofouling relies on the generable higher steric hindrance as compared with linear analogs. This study established a Dv-relevant evaluation model for acquiring an optimized antifouling surface based on the appropriate choice of polymer structure, topology morphologies, and grafting parameters.