Asparanin A inhibits cell migration and invasion in human endometrial cancer via Ras/ERK/MAPK pathway

Abstract

Asparanin A (AA), a natural compound present in vegetables and medicinal herbs like Asparagus officinalis L., has been investigated extensively for its pharmacological attributes. So far, the effect of AA on endometrial cancer (EC) cell migration and invasion has not been explored. Herein, we elucidated the anti-metastasis mechanism of AA on Ishikawa cells based on miRNA-seq and mRNA-seq integrated analyses. AA treatment led to altered miRNAs expression in Ishikawa cells and inhibited the cell wound healing, cell migration and invasion. Gene Ontology and KEGG enrichment analyses showed that the target genes of different expression miRNAs were significantly enriched in Ras, Rap1 and MAPK signaling pathways. Further verification of these changes via qRT-PCR and Western blot assays in vitro and in vivo demonstrated that AA could suppress human EC cell migration and invasion through Ras/ERK/MAPK pathway. Furthermore, top two miRNAs (miR-6236-p5 and miR-12136_R+8) and top three target genes (KITLG, PDGFD, and NRAS) were identified as functional hub miRNAs and genes through miRNA-target gene network analysis. Our data presented a holistic approach to comprehend the anti-metastatic role of AA in EC after in vitro and in vivo analyses.