Wang Sanming, Chen Xiaohang, Zhang Zhenwei, Wu Zeyu
Pharmazie. 2019 Jul 1;74(7):423-427. doi: 10.1691/ph.2019.9411.
The objective of this study was to grab the expression levels and biological function of microRNA-1225-5p in human thyroid cancer. The miR-1225-5p expression in thyroid cancer tissue and cell lines was detected, followed by detecting the effects of overexpression of miR-1225-5p on the proliferation, apoptosis, migration and invasion of thyroid cancer cells. Moreover, the target relationship between miR-1225-5p and sirtuin 3 (SIRT3) was investigated. Besides, the effect of miR-1225-5p on the activation of Wnt/β-catenin pathway was elucidated. The miR-1225-5p expression was downregulated in thyroid cancer tissues and cell lines. Overexpression of miR-1225-5p significantly inhibited TPC-1 cell proliferation, increased cell apoptosis, and suppressed migration and invasion. In addition, SIRT3 was verified as a functional target of miR-1225-5p. SIRT3 expression was overtly increased in thyroid cancer tissues and cell lines. Overexpression miR-1225-5p and SIRT3 at the same time could significantly reverse the effects of miR-1225-5p overexpression alone on the malignant phenotypes of thyroid cancer cells. Furthermore, overexpression of miR-1225-5p significantly inhibited the activation of the Wnt/β-catenin pathway, which was remarkably reversed after overexpression of SIRT3. Our data reveal that downregulation of miR-1225-5p may promote tumor cell proliferation and metastasis in thyroid cancer a direct targeting of SIRT3. Activation of the Wnt/β-catenin pathway may be a key mechanism to mediate the role of miR-1225-5p/SIRT3 axis in thyroid cancer. miR-1225-5p may serve as a potential anti-cancer target for thyroid cancer treatment.
本研究的目的是探究微小RNA-1225-5p在人类甲状腺癌中的表达水平及生物学功能。检测了甲状腺癌组织和细胞系中miR-1225-5p的表达,随后检测了miR-1225-5p过表达对甲状腺癌细胞增殖、凋亡、迁移和侵袭的影响。此外,研究了miR-1225-5p与沉默调节蛋白3(SIRT3)之间的靶向关系。此外,还阐明了miR-1225-5p对Wnt/β-连环蛋白信号通路激活的影响。甲状腺癌组织和细胞系中miR-1225-5p表达下调。miR-1225-5p过表达显著抑制TPC-1细胞增殖,增加细胞凋亡,并抑制迁移和侵袭。此外,SIRT3被证实为miR-1225-5p的功能靶点。甲状腺癌组织和细胞系中SIRT3表达明显增加。同时过表达miR-1225-5p和SIRT3可显著逆转单独过表达miR-1225-5p对甲状腺癌细胞恶性表型的影响。此外,miR-1225-5p过表达显著抑制Wnt/β-连环蛋白信号通路的激活,SIRT3过表达后这种抑制作用明显逆转。我们的数据表明,miR-1225-5p下调可能通过直接靶向SIRT3促进甲状腺癌肿瘤细胞增殖和转移。Wnt/β-连环蛋白信号通路的激活可能是介导miR-1225-5p/SIRT3轴在甲状腺癌中作用的关键机制。miR-1225-5p可能成为甲状腺癌治疗的潜在抗癌靶点。