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Previous studies have demonstrated that the aberrant expression of deubiquitinating enzymes (DUBs) is closely associated with cancer progression, including gastric cancer (GC), due to its role in maintaining protein stability. The 26S proteasome non-ATPase regulatory subunit 14 (PSMD14), a member of the DUBs family, is reported to be highly expressed in some types of cancer and its overexpression indicates poor prognosis, but the function of PSMD14 in GC remains unclear. To investigate this issue, we first analyzed the PSMD14 expression via the TNMplot database and found that PSMD14 was up-regulated in GC tissues compared with the adjacent normal tissues (P < 0.01). PSMD14 knockdown notably inhibited cell proliferation, migration, and invasion in vitro , which was confirmed through in vivo experiments. However, PSMD14 overexpression presented the opposite effects. Additionally, we found that PSMD14 deletion inhibited the protein level of polypyrimidine tract-binding protein 1 (PTBP1), an activator of GC development. Further investigation confirmed that PSMD14 and PTBP1 presented co-localization and had an endogenous interaction. PSMD14 was revealed to promote the deubiquitination and stabilization of PTBP1, and PTBP1 knockdown reversed the effects caused by PSMD14 overexpression on cell function. Collectively, we demonstrate that PSMD14 as a deubiquitinating enzyme may promote the development of GC via stabilizing PTBP1, which provides a theoretical basis for a therapeutic target against GC. • PSMD14 was highly expressed in gastric cancer (GC) samples and cell lines. • PSMD14 notably promotes GC cell proliferation, migration, invasion and the growth of xenograft tumors in vivo. • PSMD14 promotes the deubiquitination and stabilization of polypyrimidine tract-binding protein 1 (PTBP1) in GC cells. • PTBP1 mediates the promoting effect of PSMD14 on the development of GC. [ABSTRACT FROM AUTHOR]

Abstract: Formation of the neural tube is the morphological hallmark for development of the embryonic central nervous system (CNS). Therefore, neural tube development is a crucial step in the neurulation process. Slit/Robo signaling was initially identified as a chemo-repellent that regulated axon growth cone elongation, but its role in controlling neural tube development is currently unknown. To address this issue, we investigated Slit/Robo1 signaling in the development of chick neCollege of Life Sciences Biocentre, University of Dundee, Dundee DD1 5EH, UKural tube and transgenic mice over-expressing Slit2. We disrupted Slit/Robo1 signaling by injecting R5 monoclonal antibodies into HH10 neural tubes to block the Robo1 receptor. This inhibited the normal development of the ventral body curvature and caused the spinal cord to curl up into a S-shape. Next, Slit/Robo1 signaling on one half-side of the chick embryo neural tube was disturbed by electroporation in ovo. We found that the morphology of the neural tube was dramatically abnormal after we interfered with Slit/Robo1 signaling. Furthermore, we established that silencing Robo1 inhibited cell proliferation while over-expressing Robo1 enhanced cell proliferation. We also investigated the effects of altering Slit/Robo1 expression on Sonic Hedgehog (Shh) and Pax7 expression in the developing neural tube. We demonstrated that over-expressing Robo1 down-regulated Shh expression in the ventral neural tube and resulted in the production of fewer HNK-1+ migrating neural crest cells (NCCs). In addition, Robo1 over-expression enhanced Pax7 expression in the dorsal neural tube and increased the number of Slug+ pre-migratory NCCs. Conversely, silencing Robo1 expression resulted in an enhanced Shh expression and more HNK-1+ migrating NCCs but reduced Pax7 expression and fewer Slug+ pre-migratory NCCs were observed. In conclusion, we propose that Slit/Robo1 signaling is involved in regulating neural tube development by tightly coordinating cell proliferation and differentiation during neurulation. [Copyright &y& Elsevier]