OncoTargets and Therapy (Aug 2019)
miRNA-15a regulates the proliferation and apoptosis of papillary thyroid carcinoma via regulating AKT pathway
Abstract
Jin Jin,1 Jie Zhang,2 Yigui Xue,3 Li Luo,2 Siyao Wang,2 Haoming Tian11Department of Endocrinology, West China School of Medicine/West China Hospital of Sichuan University, Chengdu, Sichuan 610041, People’s Republic of China; 2Department of Endocrinology, The Fifth Affiliated Hospital of Xinjiang Medical University, Urümqi, Xinjiang 830011, People’s Republic of China; 3Teaching and Research Laboratory of Field Medical, Border Defense Training Group of Land Force Military Medical University, Changji, Xinjiang 831200, People’s Republic of ChinaAim: 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
