LncRNA H19 Promoted the Epithelial to Mesenchymal Transition and Metastasis in Gastric Cancer via Activating Wnt/β-Catenin Signaling

Abstract

Background: Due to a combination of high morbidity and lack of effective treatments, gastric cancer (GC) remains a major cause of cancer-related death all over the world. H19, as a paternally imprinted long noncoding RNA (lncRNA), has been found dysregulated in GC. Aim: The aim of this study is to elucidate the specific mechanism of H19 in GC. Methods: Bioinformatic analysis and quantitative real-time PCR analysis were utilized to test the expression pattern of H19 in GC tissues and cell lines. Wound healing, transwell, immunofluorescence assay, and Western blot assays were conducted to test cell malignant phenotypes. Meanwhile, TOP/FOP flash assay was to analyze the relationship of H19 and Wnt/β-catenin signaling. Also, mice xenograft models were to evaluate the influence of H19 on tumor growth. Results: H19 was overexpressed in GC tissues and cell lines and related to poor prognosis for GC patients. In vitro and in vivo assays verified the promotion of H19 on GC cell epithelial to mesenchymal transition (EMT) and metastasis. Mechanistically, H19 could induce β-catenin to transfer into nucleus and activate Wnt/β-catenin signaling, thus promoting EMT and metastasis of GC cells. Conclusion: Our findings proved the mechanism of H19-mediated metastasis via activating Wnt/β-catenin signaling, which provides a promising target for developing new therapeutic strategies in GC.