MicroRNA let-7c-3p inhibits proliferation, migration, and invasiveness of papillary thyroid carcinoma cells by targeting CXCL3 mRNA

INTRODUCTION: Papillary thyroid carcinoma (PTC) is the most common endocrine cancer. miRNAs are involved in the initiation and progression of PTC. There is evidence that let-7c-3p plays a suppressive role in the proliferation, migration, and invasiveness of different types of tumor cells. However, its effects on PTC cells remain unclear. MATERIAL AND METHODS: The polymerase chain reaction was used to detect let-7c-3p expression in human PTC tis­sue samples and cell lines. The proliferation ability of transfected cells was determined by CCK-8 assays. Mobility and invasion ability of transfected cells were measured by wound healing and transwell assays. The relative protein expression of transfected cells was determined by Western blot. A dual luciferase reporter assay was performed to identify the targeted binding of let-7c-3p and CXCL3. TPC-1 cells transfected with let-7c-3p were in­jected subcutaneously into the dorsal side of nude mice to observe the in vivo tumour inhibitory effect of let-7c-3p. RESULTS: The let-7c-3p was downregulated in PTC tissue samples and cell lines and negatively correlated with tumor size, lymph node metastasis, and tumor-node-metastasis stage (TNM stage). Overexpression of let-7c-3p decreases tumor size and weight in an in vivo xenograft tumor model. CXCL3 has been identified as a target gene of let-7c-3p. Overexpression of let-7c-3p inhibited PTC cell proliferation, migration, and invasion, whereas co-transfection with a CXCL3-overexpressing plasmid reversed the antitumor effects of let-7c-3p. Moreover, let-7c- -3p overexpression suppressed AKT phosphorylation and decreased AKT1, BCL-2, and MMP1 protein expression CONCLUSIONS: The results indicate a tumor-suppressive function of let-7c-3p (via CXCL3 downregulation) during PTC progression and reveal a potential therapeutic target for PTC.