MicroRNA-27b-3p inhibits the proliferation and invasion of cutaneous squamous cell carcinoma by targeting EGFR and MMP-13.

Abstract

Cutaneous squamous cell carcinoma is a common malignant tumor. The aim of the present study was to examine the biological function of microRNA (miR)-27b-3p in cutaneous squamous cell carcinoma (CSCC) and its underlying mechanism. The relative expression levels of miR-27b-3p were determined in A-431, Colo-16 and NHEK/SVTERT3-5 cell lines. The regulatory effects of miR-27b-3p on the proliferation of CSCC cells were evaluated using MTT and colony formation assays. Transwell assays were conducted to examine the role of miR-27b-5p in the migratory and invasive abilities of CSCC cells. The levels of EGFR, MMP-13, Akt, phosphorylated (p)-Akt, cyclin D1, N-cadherin (CAD) and E-CAD were detected in CSCC cells using reverse transcription-quantitative PCR and western blot analysis. Binding between miR-27b-3p and the 3'-untranslated region (UTR) of EGFR or MMP-13 was assessed using a dual-luciferase reporter assay. miR-27b-3p was significantly downregulated in CSCC cell lines, compared with the skin keratinocyte cell line. Transfection with a miR-27b-3p mimic significantly reduced the proliferative, migratory and invasive abilities of CSCC cells in vitro. Moreover, miR-27b-3p mimic transfection downregulated the mRNA and protein levels of EGFR, MMP-13, cyclin D1, p-Akt and N-CAD, whilst upregulating E-CAD levels in CSCC cells. miR-27b-3p was found to target the EGFR and MMP-13 3'-UTRs, thus downregulating the expression of these molecules. The inhibition of CSCC proliferation by miR-27b-3p was effectively reversed by EGFR overexpression. Moreover, the inhibitory effect of miR-27b-3p on the migratory and invasive abilities of CSCC cells was abolished by MMP-13 overexpression. In conclusion, miR-27b-3p inhibits the proliferation, migration and invasion of CSCC cells by downregulating the expression of EGFR and MMP-13 and may represent a potential diagnostic marker and therapeutic option for CSCC.