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Purpose: Keratin 18 (KRT18) is a cytoskeleton protein that plays a key role in multiple cancers. The present study aims to further investigate the roles of KRT18 in gastric cancer (GC) tissues and cells. Methods: The KRT18 protein expression levels of GC tissues and cells were detected using immunohistochemistry and western blot. The relationship between KRT18 expression levels and the prognosis of GC patients was further analyzed. To explore this relationship, small interfering RNA (siRNA) was used to inhibit the endogenous expression of KRT18 in GC cells. Furthermore, the effects of KRT18 on the proliferation, invasion, migration, and apoptosis of GC cells were analyzed in vitro. In addition, the role of KRT18 in GC‐specific processes was investigated. Results: Keratin 18 expression was shown to be up‐regulated in GC tissues and associated with poor prognosis. Following KRT18 silencing with siRNA, the proliferation, invasion, and migration ability of GC cells were significantly inhibited, while the apoptotic process was promoted. Furthermore, the activation of the MAPK signalling pathway was identified as the potential mechanism through which KRT18 influenced GC processes. Conclusions: Keratin 18 plays a cancer‐promoting role and might be a potential therapeutic target in the treatment of GC. [ABSTRACT FROM AUTHOR]

Background and Aim: MicroRNA-18a (miR-18a) has been reported to be upregulated in gastric cancer (GC) tissues compared with normal gastric tissues. However, little is known about its prognostic value and biological roles. Methods: In this study, miR-18a expression in gastric adenocarcinoma (GAC) tissues and adjacent non-tumor tissues was validated by in situ hybridization, and the predictive values of miR-18a were explored. The biological roles of miR-18a and the underlying signal pathway were investigated in GC cell lines. Results: Overexpressed intra-tumoral miR-18a was associated with poor survival rate and was an independent prognostic factor for overall survival rate ( P < 0.001) in GC patients. Forced expression of miR-18a remarkably enhanced cell proliferation, migration, and invasion in GC cells, while inhibition of miR-18a caused the opposite effects. Further study showed that miR-18a suppressed the expression of interferon regulatory factor 2 (IRF2) by directly binding to its 3′-untranslated region. Moreover, miR-18a expression levels are inversely correlated with IRF2 in human GC tissues. Western blot showed that forced expression of miR-18a could not only downregulate the expression of IRF2, but also inhibit the expression of P53, suggesting that IRF2 might play as a tumor suppressor by regulating P53 signaling in GC. Conclusion: miR-18a modulated P53 expression by directly targeting IRF2 and had a high predictive value for prognosis of GAC patients. These results may lead to identification of therapeutic candidates of GC. [ABSTRACT FROM AUTHOR]