MicroRNA-26a-5p inhibits proliferation, invasion and metastasis by repressing the expression of Wnt5a in papillary thyroid carcinoma

摘要

Background: Thyroid cancer (TC) is considered as the fastest growing malignancy in the human endocrine system, particularly papillary thyroid cancer (PTC). MicroRNAs (miRs) serve as a role in promoting or suppressing tumors in various types of malignant tumor including PTC. This study aims to explore whether microRNA-26a-5p (miR-26a-5p) could affect the proliferation, invasion and metastasis ability of PTC cells by regulating Wnt5a. Materials and methods: The expression of miR-26a-5p was examined by qRT-PCR in PTC tissue samples (58 cases, mean age 53 years old) and PTC cell lines (K1 and BCPAP). Cell proliferation, invasion and migration were tested with CCK8 assay, colony formation assay, transwell invasion assay and wound healing assay, respectively. Luciferase reporting experiment was used to verify that Wnt5a is a molecular target of miR-26a-5p. The relationship between miR-26a-5p and Wnt5a was analyzed by qRT-PCR and Western blot and was further proved by Pearson’s correlation analysis. Animal (24 nude mice) experiments were used to demonstrate that miR-26a-5p inhibits tumor growth by targeting Wnt5a. Results: The expression of miR-26a-5p declined in PTC tissues ( P 0.01). The expression of miR-26a-5 was also significantly down-regulated in PTC tissues with advanced TNM stages ( P 0.01) and lymph node metastasis ( P 0.01) compared with normal thyroid tissues.?Compared with normal human thyroid cell line Nthy-ori 3-1, the expression of miR-26a-5p in K1 cells and BCPAP cells were nearly 4.02-fold ( P 0.01) and 2.51-fold ( P 0.01) reduced. Up regulation of miR-26a-5p inhibited proliferation, colony formation, invasion and migration of PTC cells. MiR-26a-5p negatively regulated Wnt5a expression ( r =?0.887, P 0.01), yet Wnt5a overexpression reversed the tumor-suppressive effect of miR-26a-5p in PTC. Animal experiments further verified that miR-26a-5p inhibited PTC growth by targeting Wnt5a. Conclusion: Overexpression of miR-26a-5p depresses proliferation, invasion, metastasis of PTC via Wnt5a. Therefore, miR-26a-5p may represent a potentially effective target gene for PTC.