Transcription activation of microRNA-25 by PEA3 augments progression of gastric cancer through suppressing SIK1.

NEW FINDINGS What is the central question of this study? What is the function of miR-25 in the development of gastric cancer (GC) and the molecular mechanism? What is the main finding and its importance? Polyomavirus enhancer activator protein 3 (PEA3) activates transcription of microRNA-25 and augments progression of GC through suppressing salt-inducible kinase 1 (SIK1) and activating the Wnt/β-catenin pathway. ABSTRACT Gastric cancer (GC) is one of the leading causes of cancer-related death worldwide. Aberrant expression of microRNAs (miRNAs) is frequently involved in the pathogenesis of GC. This study aims to determine the functions of miR-25 in GC development and the molecular mechanism. miR-25 was screened to be significantly highly expressed in GC tissues using a miRNA microarray analysis. The subsequent RT-qPCR suggested high-expression profiling of miR-25 in cancer tissues and cells relative to the normal samples. High miR-25 expression indicated poor prognosis and shorter survival time of GC patients. Polyomavirus enhancer activator protein 3 (PEA3) was identified as an upstream transcriptional activator of miR-25. miR-25 directly bound to salt-inducible kinase 1 (SIK1) mRNA. Downregulation of miR-25 suppressed proliferation and invasiveness of GC cells and the growth of xenograft tumors in vivo. These tumor-suppressive effects were strengthened by further silencing of PEA3 but blocked by SIK1 knockdown. The PEA3/miR-25 axis was found to activate the Wnt/β-catenin signaling pathway. To conclude, this study suggested that PEA3 activates miR-25 transcription and regulates GC progression through suppressing SIK1 and activating the Wnt/β-catenin pathway. This study may provide new ideas in GC treatment. This article is protected by copyright. All rights reserved.