Importin-4 functions as a driving force in human primary gastric cancer

Importin-4 (IPO4) is responsible for transporting histones H3 and H4 into the nucleus for chromatin assembly. But, the role of IPO4 in cancer, especially in gastric cancer (GC), has not been fully understood. We aim to determine the expression and function of IPO4 in GC.

Bioinformatics analysis was used to study the association of IPO4 and GC using GEO data and the Kaplan-Meier plotter. The quantitative real-time polymerase chain reaction and Western blot analysis were used to determine the IPO4 level in GC cells and tissues. Small interfering RNAs (siRNAs) were used to knockdown endogenous IPO4 expression in GC cells. Cell counting kit-8 (CCK-8), colony formation and transwell assays were used to examine the effect of IPO4 on cell proliferation and migration.

IPO4 mRNA is overexpressed in GC tissues using bioinformatics analysis of three groups' transcriptome data, and high level of IPO4 is negatively correlated with poor long-term survival using the Kaplan-Meier plotter analysis. Western blot analysis further shows that IPO4 protein levels are also overexpressed in GC tissues and a number of GC cell lines. Endogenous IPO4 level can be inhibited by specific siRNA effectively. Importantly, CCK-8, colony formation, and transwell assays demonstrate that IPO4 knockdown by siRNA impairs GC cell proliferation and migration.

Our data suggest that IPO4 contributes to GC progression and poor prognosis, and may function as a driving force in GC progression.