Tumor-derived Exosomal LncRNA SNHG16 Induces Telocytes to promote metastasis of hepatocellular carcinoma via miR-942-3p/MMP9 axis

Abstract Background: Hepatocellular carcinoma(HCC) cells-derived exosomal LncRNA SNHG16(LncSNHG16) is highly expressed and associated with the poor overall survival of patients. Telocytes(TCs), as novel interstitial cells, possess the function to promote HCC metastasis. Therefore, whether a molecular interaction between exosomal LncSNHG16 and TCs will be revealed in our study.Methods: LncSNHG16 expression in HCC tissues and cell lines were detected, and its bioinformatics analysis was screened. Exosomes were isolated and purified from HCC cells with over-expressed/knockdown LncSNHG16 vectors and co-cultured with TCs. Then, the expression of the LncSNHG16/miR-942-3p/MMP9 axis was tested in TCs. Transwell and cell wound healing assays were designed to examine the invasion and migration of HCC cells after co-incubating with TCs. RNA immunoprecipitation(RIP) assay and Dual-Luciferase gene report were utilized to verify the binding effect of LncSNHG16, miR-942-3p, and MMP9 mRNA. In vivo, experimental animal models were established to confirm the effect of exosomal LncSNHG16-induced MMP9 expression in HCC metastasis.Results: Exosomal LncSNHG16 could be phagocytized by TCs and down-regulated miR-942-3p, which induced the targeted MMP9 up-regulation. LncSNHG16 had special binding sites with miR-942-3p in TCs to facilitate the migration of HCC cells in vitro and in vivo. Exosomal LncSNHG16 was finally supported as competing endogenous RNA of the miR-942-3p/MMP9 axis in TCs.Conclusion: Tumor-derived exosomal LncSNHG16 modulates MMP9 by competitively binding to miR-942-3p in TCs, thus promoting the metastasis of HCC.