MiR-144-3p promotes the tumor growth and metastasis of papillary thyroid carcinoma by targeting paired box gene 8

摘要

Paired box gene 8 (PAX8) is expressed in and indispensable to thyroid development. MiR-144-3p is found dys-regulated in cancers, and it can block the expression of target gens. This study sought to understand the effect of MiR-144-3p in papillary thyroid carcinoma (PTC) as well as the associated mechanisms. Real-time PCR, immunohistochemical and Western blot assays were performed to examine the expression of target miRNA and/or genes. CCK-8 and flow cytometry analysis was used to respectively test cell growth, cell cycle progression and apoptosis. Luciferase reporter assay was performed to find out whether miR-144-3p could bind to the 3′ untranslated region of PAX8 or not. We found that PAX8 decreased in PTC, while miR-144-3p increased in PTC. Over-expression of miR-144-3p promoted the cell viability and cell cycle progression. The expressions of cell-cycle-related genes, cyclin D1, cyclin-dependent kinase 2 and CDC25A were modulated by miR-144-3p. Meanwhile, the presence or absence of miR-144-3p both affected epithelial-mesenchymal transition of PTC by regulating the expression of E-cadherin, N-cadherin and vimentin. Moreover, PAX8 may be a potential direct target of miR-144-3p. Mechanically, the activation of extracellular signal–regulated kinases 1/2, Akt and c-Jun N-terminal kinases may be associated with the tumor-promoting effect of miR-144-3p. In addition, the blockage of miR-144-3p forced the anti-tumor effect delivered by X-ray exposure or paclitaxel. MiR-144-3p promoted the growth of tumor and the metastasis of PTC by targeting PAX 8. The study provided promising prognosis markers and valuable treatment strategy for PTC.