MicroRNA‑335 is downregulated in papillary thyroid cancer and suppresses cancer cell growth, migration and invasion by directly targeting ZEB2

Abstract

MicroRNAs (miRs) are a group of short, endogenous, non-protein-coding and single-stranded RNAs that regulate gene expression by binding to the 3'-untranslated region (3'UTR) of mRNAs, which results in their degradation or translational repression. The aim of the present study was to investigate the expression and function of miR-335 in human papillary thyroid cancer (PTC). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to quantify the relative miR-335 expression levels in PTC tissues and cell lines. The effect of miR-335 on the proliferation, migration and invasion of PTC cells was assessed by an MTT assay, and transwell migration and invasion assays, respectively. Dual-luciferase reporter assays were employed to explore whether miR-335 directly targeted the 3'UTR of the potential target gene zinc finger E-box binding homeobox 2 (ZEB2). RT-qPCR and western blotting were adopted to assess the effect of miR-335 on the mRNA and protein expression of ZEB2. RT-qPCR revealed that miR-335 was downregulated in PTC tissues and cell lines. The MTT assay and transwell migration and invasion assays demonstrated that the overexpression of miR-335 significantly inhibited the proliferation, migration and invasion of PTC cells. ZEB2 was identified as a direct target of miR-335 with computational analysis, which was confirmed with a dual-luciferase reporter assay, RT-qPCR and western blotting. The knockdown of ZEB2 significantly inhibited the proliferation, migration and invasion of PTC cells, indicating that ZEB2 may be a functional target of miR-335. Taken together, these findings suggested that miR-335 functioned as a tumor suppressor and suppressed the growth and metastatic behavior of PTC cells by targeting ZEB2.