TMED5 Promotes the Progression of Gastric Cancer through Activation of the HIF-1α/Wnt/β-Catenin Pathway

Abstract

Background: The present research sought to figure out the expression features and role of transmembrane p24 trafficking protein 5 (TMED5), a novel oncogene, in gastric cancer (GC). Materials and Methods: Firstly, reverse transcription-polymerase chain reaction (RT-PCR) and Western blot (WB) were implemented to monitor the TMED5 level in GC tissues and paracancerous non-tumor tissues and the link between the TMED5 profile and clinical-pathological parameters of the patients was probed. Secondly, TMED5 knockdown models were established in AGS and MKN-45 cells. Then, the cell counting kit-8 (CCK-8) and colony formation experiments were utilized to check cell proliferation. Afterward, the expression of apoptosis-related proteins and the hypoxia-inducible factor-1alpha (HIF-1α)/Wnt/β-catenin axis were gauged by WB. Subsequently, Transwell assay monitored cell invasion. Results: TMED5 was highly expressed in GC tissues versus adjacent paracancerous tissues, and the high TMED5 expression was strongly linked to undesirable GC prognosis. Knocking down TMED5 choked GC cell proliferation and invasion and facilitated apoptosis. In vivo, the tumorigenic ability of GC cells knocking down TMED5 was obviously dampened. Mechanism studies have confirmed that knocking down TMED5 notably inactivated the HIF-1α/Wnt/β-catenin axis. Moreover, the TMED5 knockdown-mediated anti-tumor effect was largely abated after attenuating the HIF-1α pathway by LW6. Conclusions: This study substantiated that TMED5 is up-regulated in GC tissues and affects GC advancement by modulating the HIF-1α/Wnt/β-catenin pathway.