miR‐4725‐3p targeting stromal interacting molecule 1 signaling is involved in xanthohumol inhibition of glioma cell invasion

摘要

Abstract Glioblastoma multiforme is the most common brain tumor in adults. Because of its highly invasive nature, it is not easy to treat, resulting in high mortality rates. Stromal interacting molecule 1 (Stim1) plays important roles in regulating storeoperated Ca2+ entry, and controls invasion by cancer cells. However, the mechanisms and functions of Stim1 in glioma progression are still unclear. In this study, we investigated the effects of targeting Stim1 expression on glioma cell invasion. By analyzing profiles of glioblastoma multiforme patients fromRNA sequencing data in The Cancer Genome Atlas, higher expression levels ofSTIM 1were correlated with the poor survival. Furthermore, signaling pathways associated with tumor malignancy, including the epithelialtomesenchymal transition (EMT ), were activated in patients with highSTIM 1expression according to gene set enrichment analyses. Higher Stim1 levels were found in glioma cells compared to human astrocytes, and these higher levels enhanced glioma cell invasion. Xanthohumol (XN ), a prenylated flavonoid extracted from the hop plantHumulus lupulus L . (Cannabaceae), significantly reduced cell invasion through inhibiting Stim1 expression. From an micro(mi)RNA array analysis, miR47253p was upregulated byXN treatment. Overexpression of miR47253p inhibited glioma cell invasion via directly targeting the 32untranslated region ofSTIM 1. The extracellular signalregulated kinase/cFos pathway was also validated to participate inXN upregulated miR47253p expression according to promoter and chromatin immunoprecipitation assays. These results emphasize that miR47253pinhibitedSTIM 1 signaling is involved inXN attenuated glioma cell invasion. These findings may provide insights into novel therapeutic strategies for future glioblastoma therapy and drug development.Open Data: Materials are available onhttps://cos.io/our-services/open-science-badges/ https://osf.io/93n6m/