MicroRNA-223-3p stimulates proliferation, metastasis and regulates cell cycle via downregulating Neurofibromatosis Type 2 in Papillary thyroid cancer

Papillary thyroid carcinoma (PTC) has become one of malignant diseases of endocrine system with the highest incidence rate especially among women. MicroRNA performed different roles in various cancer. MicroRNA-223-3p has been demonstrated to be highly transcribed in various cancerous cells to regulate tumor development. But the performance of microRNA-223-3p in PTC proliferation and metastasis is still unclear. Therefore, microRNA-223-3p and its predicted targeting protein NF-2 were examined in PTC tissues and cells by RT-qPCR and/or western blot assay. CCK-8 assay and transwell assay were carried out to evaluate the regulatory effect on cell proliferative and invasion respectively. Western blot was performed to evaluate N-cadherin, E-cadherin, Vimentin, MMP2 and MMP9 expression.Luciferase reporter assay has been achieved for examining the targeting sites in microRNA-223-3p with 3’UTR of NF-2. Moreover, the xenografts nude mice were utilized for accessing the roles of microRNA-223-3p on tumor increasing and KI-67 expression. According to our results, microRNA-223-3p was upregulated in PTC tissues and cells. The highly expression of microRNA-223-3p is related with poor prognosis in PTC patients. Moreover microRNA-223-3p mimics stimulates cell proliferative and invasive abilities in TPC-1 cells. And microRNA-223-3p could also induce the EMT of TPC-1 cells and up-regulate the expression of MMP2 and MMP9. Furthermore, luciferase reporter assays showed microRNA-223-3p can directly target NF-2 in TPC-1 cells. In addition, NF-2 overexpression could partially reverse the regulatory roles of microRNA-223-3p on PTC cell proliferation, invasion and EMT. The promotion impact of microRNA-223-3p on PTC cell was also confirmed through in vivo experiment. Therefore, microRNA-223-3p becomes a potential marker of PTC prognosis and microRNA-223-3p promotes the cell duplication and invasion through downregulating NF-2 in PTC cell lines. The discovery of microRNA-223-3p/NF-2 axis might pave a new way on the pathogenesis and therapy of PTC.