RETRACTED ARTICLE: M2 macrophage-derived extracellular vesicles promote gastric cancer progression via a microRNA-130b-3p/MLL3/GRHL2 signaling cascade

Journal of Experimental & Clinical Cancer Research

Research

Xun Li¹  Ping Yue²  Wenbo Meng²  Yu Zhang³ 

[1] The First Clinical Medical School of Lanzhou University, 730000, Lanzhou, Gansu Province, People’s Republic of China;Department of General Surgery, The First Hospital of Lanzhou University, No. 1, Donggang West Road, Chengguan District, 730000, Lanzhou, Gansu Province, People’s Republic of China;The First Clinical Medical School of Lanzhou University, 730000, Lanzhou, Gansu Province, People’s Republic of China;Department of Special Minimally Invasive Surgery, The First Hospital of Lanzhou University, 730000, Lanzhou, People’s Republic of China;The First Clinical Medical School of Lanzhou University, 730000, Lanzhou, Gansu Province, People’s Republic of China;Department of Thoracic Surgery, The First Hospital of Lanzhou University, 730000, Lanzhou, People’s Republic of China;

关键词: Gastric cancer;    microRNA-130b-3p;    M2 macrophages;    Extracellular vesicles;    MLL3;    GRHL2;   

DOI  :  10.1186/s13046-020-01626-7

 received in 2020-02-19, accepted in 2020-06-21,  发布年份 2020

来源: Springer

【 摘 要 】

BackgroundTransfer of noncoding microRNAs (miRNAs) by extracellular vesicles (EVs) promotes the development of chemoresistance in many tumor types. Additionally, restoration or depletion of several miRNAs has been observed in multiple cancer types including gastric cancer (GC). In this present study, we aimed to investigate the mechanism of miR-130b-3p in M2 macrophage-derived EVs in the development of GC through regulation of mixed lineage leukemia 3 (MLL3) and grainyhead-like 2 (GRHL2).MethodsExpression of miR-130b-3p and GRHL2 was quantified in 63 pairs of cancerous and noncancerous gastric tissues. The predicted binding between miR-130b-3p and MLL3, together with the enrichment of MLL3, H3K4me1, and H3K27ac in gene enhancer region, was verified by luciferase activity assay and chromatin immunoprecipitation. Effects of miR-130b-3p on GC cell proliferation, apoptosis, migration and invasion, as well as tube formation of human umbilical endothelial vein cells (HUEVCs) were further determined by gain- and loss-of function assays in vitro.ResultsmiR-130b-3p was upregulated in GC tissues, and miR-130b-3p promoted survival, metastasis and angiogenesis of GC cells as well as enhanced tumor formation and angiogenesis in GC in vivo. Additionally, miR-130b-3p delivered in M2 macrophage-derived EVs promoted survival, migration, invasion, and angiogenesis of GC cells. Notably, MLL3 inhibited GC cell proliferation, migration, invasion, and vessel-like tube formation of HUEVCs by increasing GRHL2. Furthermore, downregulation of miR-130b-3p in M2 macrophage-derived EVs or upregulation of GRHL2 inhibited tumor formation and angiogenesis in GC.ConclusionThis study highlights that EVs loaded with the specific miRNA cargo miR-130b-3p mediate communication between M2 macrophages and cancer cells in the tumor microenvironment through the modulation of MLL3 and GRHL2 in GC.

【 授权许可】

CC BY   
© The Author(s). 2020

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