Aim: Aberrantly expressed microRNAs (miRNAs) are involved in many diseases including cancer. The expression of miR-15a was reported to be downregulated in papillary thyroid carcinoma (PTC) compared to control tissue. However, the mechanism underlying this downregulation remains unclear.
Methods: The effects of miR-15a on the proliferation and invasion of PTC cells were evaluated by CCK-8 and transwell assays, respectively. Expression levels of AKT and rearranged during transfection (RET) in cells were assessed using Western blotting. The correlation of RET and miR-15a was validated by luciferase reporter assay. Moreover, in vivo assay was performed to demonstrate the effect of miR-15a on tumor growth.
Results: We confirmed that the expression of miR-15a was significantly lower in PTC tissue than that in normal tissue. Overexpression of miR-15a notably inhibited PTC cell proliferation and invasion via promoting apoptosis. Additionally, RET was found to be a target of miR-15a and this correlation was confirmed by dual-luciferase assay and Western blot. Furthermore, in vivo study revealed that overexpression of miR-15a inhibited tumor growth via downregulating the levels of RET and phosphorylated AKT.
Conclusion: In the present study, we demonstrated that miR-15a played an antitumor role in regulating PTC via targeting RET/AKT pathway. Therefore, miR-15a may serve as a potential molecular target for the treatment of PTC.
Keywords: miRNA-15a, papillary thyroid carcinoma, AKT pathway, apoptosis