Jin Jin, Zhang Jie, Xue Yigui, Luo Li, Wang Siyao, Tian Haoming
Department of Endocrinology, West China School of Medicine/West China Hospital of Sichuan University, Chengdu, Sichuan 610041, People's Republic of China.
Department of Endocrinology, The Fifth Affiliated Hospital of Xinjiang Medical University, Urümqi, Xinjiang 830011, People's Republic of China.
Onco Targets Ther. 2019 Aug 6;12:6217-6226. doi: 10.2147/OTT.S213210. eCollection 2019.
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.
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.
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.
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.
异常表达的微小RNA(miRNA)参与包括癌症在内的多种疾病。据报道,与对照组织相比,乳头状甲状腺癌(PTC)中miR-15a的表达下调。然而,这种下调的潜在机制仍不清楚。
分别通过CCK-8和Transwell实验评估miR-15a对PTC细胞增殖和侵袭的影响。使用蛋白质免疫印迹法评估细胞中AKT和转染重排(RET)的表达水平。通过荧光素酶报告基因实验验证RET与miR-15a的相关性。此外,进行体内实验以证明miR-15a对肿瘤生长的影响。
我们证实,PTC组织中miR-15a的表达明显低于正常组织。miR-15a的过表达通过促进细胞凋亡显著抑制PTC细胞的增殖和侵袭。此外,发现RET是miR-15a的靶标,双荧光素酶实验和蛋白质免疫印迹法证实了这种相关性。此外,体内研究表明,miR-15a的过表达通过下调RET和磷酸化AKT的水平抑制肿瘤生长。
在本研究中,我们证明miR-15a通过靶向RET/AKT途径在调节PTC中发挥抗肿瘤作用。因此,miR-15a可能作为治疗PTC的潜在分子靶点。