MiR-4500 Regulates PLXNC1 and Inhibits Papillary Thyroid Cancer Progression

Abstract

Although most patients with papillary thyroid cancer (PTC) are curable, there are still a few patients showing poor outcomes and increased risk of secondary cancers after therapies. In this study, we aimed to investigate the correlation between miR-4500 and PTC and to explore its molecular functions. A total of 50 patients were included, and sonography and histological examinations were used for diagnosis. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied for detection of mRNA levels while Western blotting was used for measuring protein expression. Cell proliferation was tested using CCK-8 and colony formation assays. Caspase-3 activity and nucleosomal fragmentation assays were employed to test cell apoptosis. Cell invasive ability was measured using transwell assay. MiR-4500 target was identified using luciferase assay and RNA pull-down assay. MiR-4500 expression was significantly decreased in five PTC cell lines compared with Nthy-ori 3-1 cells and in PTC tissues compared with adjacent normal thyroid tissues, respectively. Decreased expression of miR-4500 showed lower survival rate, higher cancer stage, and lymphatic metastasis. Therefore, our results implied that miR-4500 could serve as a potential biomarker for PTC prognosis. Overexpression of miR-4500 repressed colony formation, proliferation, and invasiveness of PTC cells whereas increased cell apoptosis. We identified that PLXNC1 was a direct target of miR-4500. PLXNC1 knockdown showed similar effects on cell viability, colony formation, and cell apoptosis as overexpression of miR-4500 in PTC cells. In conclusion, miR-4500 inhibits the malignant transformation of PTC cells by directly targeting and repressing PLXNC1.