MiR-126 in Extracellular Vesicles Derived from Hepatoblastoma Cells Promotes the Tumorigenesis of Hepatoblastoma through Inducing the Differentiation of BMSCs into Cancer Stem Cells. (29th October 2021)

• Record Type: Journal Article
• Authors: Hu, Yu; Zai, Hongyan; Jiang, Wei; Yao, Yuanbing; Ou, Zhenglin; Zhu, Qin
• Other Names: Wang Shengjun Academic Editor.
• Is Part Of: Journal of immunology research. Volume 2021(2021)
• Publication Date: 2021-10-29
• Subjects: Immunology -- Periodicals; Immunology -- Research -- Periodicals; 616.07905
• DOI: 10.1155/2021/6744715
• Languages: English
• ISSNs: 2314-8861

Abstract

Abstract : Background . Extracellular vesicles (EVs) can deliver miRNAs between cells and play a crucial role in hepatoblastoma progression. In this study, we explored the differentially expressed miRNAs related to tumor cell-derived EVs and the mechanism by which EVs regulate hepatoblastoma progression. Methods . Bioinformatics analysis was performed to explore the differentially expressed miRNAs between the hepatoblastoma and adjacent normal tissues. TEM, NTA, and western blotting were conducted to identify EVs. The expression of miR-126-3p, miR-126-5p, miR-30b-3p, miR-30b-3p, SRY, IL-1 α, IL-6, and TGF- β was detected by RT-qPCR. Immunofluorescence (IF) was used to analyze the expression of PKH67, and flow cytometry was applied to assess the ratio of CD44+ CD90+ CD133+ cells. ELISA was used to evaluate the levels of IL-6 and TGF- β . A xenograft mouse model was constructed to detect the function of EVs with downregulated miR-126. IHC was performed to calculate β -catenin levels in tumor tissues. Results . miR-126 was upregulated in hepatoblastoma. EVs derived from hepatoblastoma cells significantly increased the ratio of CD44+ CD90+ CD133+ cells and increased the expression of IL-6, Oct4, SRY, and TGF- β in bone marrow mesenchymal stem cells (BMSCs), while EVs with downregulated miR-126 reversed these phenomena. miR-126 downregulation notably attenuated hepatoblastoma tumor growth and decreased the ratio of CD44+ CD90+ CD133+ cells and increased the expression of IL-6, Oct4, SRY, TGF- β, and β -catenin in tumor tissues of mice. Furthermore, EVs with downregulated miR-126 inhibited the differentiation of BMSCs into cancer stem cells. Conclusions . Exosomal miR-126 derived from hepatoblastoma cells promoted the tumorigenesis of liver cancer through inducing the differentiation of BMSCs into cancer stem cells.