MiR-451a suppresses papillary thyroid cancer cell proliferation and invasion and facilitates apoptosis through targeting DCBLD2 and AKT1

Abstract

Papillary thyroid cancer (PTC) is a common malignancy. MicroRNAs (miRNAs) may act as oncogenes or tumor suppressor genes. However, the role of miR-451a in PTC is not fully understood. Hence, the objective of the study was to research the effect and mechanism of miR-451a in PTC. Differentially expressed miRNAs between GSE113629 and GSE103996 databases were assessed by Venn diagram. miR-451a and its downstream target genes were assessed by RT-PCR and Western blot. The proliferation, invasion, and apoptosis were determined by CCK-8, EdU, transwell, and flow cytometry assays. Dual-luciferase reporter assay were used to evaluated the target of miR-451a. Xenografted tumors was used to explore the function of miR-451a in vivo. Pathological changes and related protein expression were measured by HE staining and immunohistochemistry. MiR-451a was downregulated in PTC tissues and blood, and low expression of miR-451a was related to short overall survival, serious lymph node metastasis and high TNM grade in PTC patients. Moreover, increase of miR-451a restrained the proliferation and invasion and accelerated the apoptosis. Furthermore, miR-451a repressed VEGF signaling pathway. Importantly, miR-451a was demonstrated to target DCBLD2 and AKT1. Overexpression of DCBLD2 and AKT1 could restore the effect of miR-451a on PTC cells. In addition, miR-451a reduced the growth of xenografted tumors in vivo. The data suggested that miR-451a attenuated the proliferation, invasion and promoted apoptosis in PTC cells via inhibiting DCBLD2 and AKT1.