Tumor-derived exosomes orchestrate the microRNA-128-3p/ELF4/CDX2 axis to facilitate the growth and metastasis of gastric cancer via delivery of LINC01091.

Abstract

It has been manifested that tumor-derived exosomes (Exos) can deliver long noncoding RNAs to participate in gastric cancer (GC) progression. In this research, we intended to dissect out whether tumor-derived Exos carried LINC01091 to afflict the growth and metastasis of GC. GC tissues and human GC cells were attained for RNA and protein quantification. Accordingly, LINC01091, ELF4, and CDX2 were abundant but microRNA (miR)-128-3p was underexpressed in GC tissues and cells. Exos were isolated from LINC01091-silenced GC cells (Exo-sh-LINC01091). GC cells were co-cultured with Exo-sh-LINC01091 or manipulated with miR mimic, inhibitor, or overexpressing or silencing plasmids. Exo-sh-LINC01091, LINC01091, ELF4 or CDX2 silencing, or miR-128-3p upregulation augmented GC cell proliferative, migrating, and invasive properties. In addition, luciferase, RNA pull-down, and ChIP assays offered evidence supporting the mechanism that LINC01091 bound to miR-128-3p that inversely targeted ELF4, and ELF4 transcriptionally activated CDX2 by binding to its promoter in GC cells. Moreover, Exo-sh-LINC01091 modulated the miR-128-3p/ELF4/CDX2 axis and restrained the tumorigenesis and metastasis in vivo. Conclusively, LINC01091 shuttled by tumor-derived Exos might expedite GC development by activating the ELF4/CDX2 axis via miR-128-3p downregulation.

• Authors: Qiang Wang, Chunmei Zhang, Shengya Cao, Hongying Zhao, Rongke Jiang, Yanfang Li
• Journal: Cell biology and toxicology (Cell Biol Toxicol) Vol. 39 Issue 2 Pg. 519-536 (04 2023) ISSN: 1573-6822 [Electronic] Switzerland
• PMID: 35674868 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s), under exclusive licence to Springer Nature B.V.

Chemical References

• MicroRNAs
• ELF4 protein, human
• DNA-Binding Proteins
• Transcription Factors
• CDX2 protein, human
• CDX2 Transcription Factor
• MIRN128 microRNA, human

Topics

• Humans
• MicroRNAs (genetics, metabolism)
• Stomach Neoplasms (metabolism)
• Exosomes (genetics, metabolism)
• Cell Proliferation (genetics)
• Cell Line, Tumor
• Gene Expression Regulation, Neoplastic (genetics)
• DNA-Binding Proteins (genetics, metabolism)
• Transcription Factors (genetics, metabolism)
• CDX2 Transcription Factor (genetics, metabolism)