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Cutaneous squamous cell carcinoma-derived exosomal MicroRNA-31 acts as an oncogene by targeting the tumor suppressor RhoBTB1

Mu Yanan,Lian Chen,Chen Xinghui,Yang Xueying,Li Dongxia,Zhang Yi

Tumor-derived exosomes that transport MicroRNAs significantly influence cutaneous squamous cell carcinoma(CSCC) progression. However, the molecular mechanisms of exosomal MicroRNA-31 regulation of CSCC are mostly undefined. To determine whether a targeting relationship exists between MicroRNA-31 (miR-31) in CSCC-derived exosomes and the tumor suppressor RhoBTB1, and the regulatory effect of the relationship on tumor cells. Immunoblotting and quantitative PCR were used to measure miR-31 and RhoBTB1 levels in various cells and exosomes. Differential ultracentrifugation was used to isolate exosomes. MTT and Transwell assays were used to assess cell proliferation, migration, and invasion. Dual luciferase reporter assays were used to assess the direct interaction between miR-31 and the tumor suppressor RhoBTB1 in cutaneous squamous cell carcinoma (CSCC)-derived exosomes. Compared with a human skin keratinocyte cell line, in CSCC cell lines RhoBTB1 was downregulated and miR-31 levels were elevated. Exosomal miR-31 from CSCC cell lines directly targeted RhoBTB1 by binding to the 3’ UTR of RhoBTB1. This interaction suppressed expression of RhoBTB1 and enhanced CSCC cell proliferation, migration, and invasion. MicroRNA-31 in CSCC-derived exosomes can enhance CSCC cell proliferation, migration, and invasion by suppressing expression of RhoBTB1. This finding explains, in part, the molecular mechanism of CSCC. Investigative approaches focused on suppressing miR-31 or enhancing RhoBTB1 signaling pathways are promising avenues for developing targeted therapies for CSCC.