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.
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Qiang Wang and Chunmei Zhang contributed to the conception and design of the study; Hongying Zhao and Shengya Cao contributed to the acquisition of data; Rongke Jiang and Yanfang Li contributed to the analysis and interpretation of data; Qiang Wang, Chunmei Zhang, and Hongying Zhao contributed to drafting the article; Shengya Cao and Rongke Jiang contributed to revising the article critically for important intellectual content; all of the authors approved the final version to be submitted.
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The current study was approved by the Ethics Committee of Xuzhou Cancer Hospital, Xuzhou Third People’s Hospital. Animal experiments were conducted under the approval of Animal Ethics Committee of Xuzhou Cancer Hospital, Xuzhou Third People’s Hospital.
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Wang, Q., Zhang, C., Cao, S. et al. Tumor-derived exosomes orchestrate the microRNA-128-3p/ELF4/CDX2 axis to facilitate the growth and metastasis of gastric cancer via delivery of LINC01091. Cell Biol Toxicol 39, 519–536 (2023). https://doi.org/10.1007/s10565-022-09728-y
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DOI: https://doi.org/10.1007/s10565-022-09728-y