Elp3 activates the JNK/MAPK pathway through histone acetylation to promote gastric cancer proliferation, migration, and invasion

Background: Gastric Cancer (GC) seriously affects the life and health of patients, and the role of Elp3 in GC is still unclear; therefore, the aim of this study was to investigate the role and mechanism of Elp3 overexpression in GC.

Methods: Elp3-overexpressing HGC27 cells were constructed with an overexpression plasmid, and Elp3-overexpressing GC nude mice were prepared, which were intervened by histone acetylation inhibitor (SAHA) or JNK pathway inhibitor (SP600125). The protein interactions between Elp3 and JNK1 were verified by Co-immunoprecipitation (Co-IP) assay. Cell proliferation, migration, invasion, JNK/MAPK pathway, and histopathological changes were evaluated with CCK-8, clone formation assay, scratch assay, Transwell, qRT-PCR, western blot, and HE staining.

Results: Elp3 interacted with JNK1 protein, and Elp3 overexpression promoted GC proliferation, invasion, migration, elevated HAT activity, and activation of the JNK/MAPK pathway. A histone acetylation inhibitor attenuated the promotional effect of Elp3 overexpression on GC and activation of the JNK/MAPK pathway. Further, inhibition of the JNK/MAPK pathway also suppressed the promotion of GC by Elp3 overexpression.

Conclusion: Elp3 may be involved in GC progression by activating the JNK/MAPK pathway through histone acetylation.