Let-7b miRNA-loaded nanostructures inhibited human tongue squamous cell carcinoma metastasis by the MOR-SRC-EGFR axis

[Display omitted] •Let-7b miRNA inhibited TSCC metastasis.•Let-7b miRNA modulated MOR-SRC-EGFR axis in TSCC.•Let-7b miRNA mimics were encapsulated in the endosomal pH-responsive NPs.•Systemic delivery of Let-7b miRNA mimics inhibited TSCC metastasis in vivo. miRNA is a type of classic non-coding RNA which is enriched in cancer. Various studies reported that miRNA be involved in the progression and metastasis of TSCC. Exploring pivotal miRNAs and elaborating the mechanisms inducing metastasis are important for improving the prognosis of TSCC patients. Here, Let-7b miRNA was identified as a significant factor contributing to metastasis of TSCC via directly targeting the 3′UTR of MOR mRNA, which leads to abnormally high expression of MOR protein. MORmightbindwithSRCandpotentiallyactivatep-EGFRthroughSRC. As a treatment modality, Let-7b miRNA mimics were encapsulated into the endosomal pH-responsive nanoparticles. NPs (Let-7b miRNA mimics) significantly inhibited Cal27 cells in vitro and in vivo metastatic model. Altogether, our data revealed that Let-7b miRNA-MOR-SRC-EGFR axis might be an effective therapeutic target in TSCC metastasis.