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微小RNA-574-5p通过抑制Quaking蛋白的表达,经由Wnt/β-连环蛋白信号传导途径介导甲状腺癌细胞的细胞周期和凋亡。

MiR-574-5p mediates the cell cycle and apoptosis in thyroid cancer cells via Wnt/β-catenin signaling by repressing the expression of Quaking proteins.

作者信息

Zhang Zhejia, Li Xinying, Xiao Qian, Wang Zhiming

机构信息

Department of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.

Department of Mental Hygiene Clinics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.

出版信息

Oncol Lett. 2018 Apr;15(4):5841-5848. doi: 10.3892/ol.2018.8067. Epub 2018 Feb 15.

Abstract

Thyroid cancer is the most frequently occurring type of endocrine tumor, with a rapidly increasing incidence rate. MicroRNA (miR)-574-5p is a candidate oncogene in various types of cancer. The present study identified that miR-574-5p affected the cell cycle distribution and apoptosis of BCPAP and FTC133 thyroid cancer cells via β-catenin/Wnt signaling by targeting Quaking proteins (QKIs). An MTT assay demonstrated that the knockdown of miR-574-5p suppressed the proliferation of the thyroid cancer cells. Fluorescence-activated cell sorting analysis demonstrated that the inhibition of miR-574-5p induced the G/S phase arrest and apoptosis of the cells. Reverse transcription-quantitative polymerase chain reaction and western blot analyses revealed that the knockdown of miR-574-5p significantly upregulated the mRNA and protein expression levels of QKIs. Furthermore, western blot analysis identified that the knockdown of miR-574-5p also repressed the Wnt/β-catenin pathway via downregulating the expression of β-catenin, cyclin D1 and survivin, and upregulating the phosphorylation of β-catenin. The further depletion of QKIs in combination with the knockdown of miR-574-5p not only increased the expression of β-catenin, cyclin D1 and survivin, but also rescued the apoptosis of thyroid cancer cells induced by the miR-574-5p knockdown. In conclusion, these findings indicated that the aberrant upregulation of miR-574-5p may be oncogenic, through regulating the Wnt/β-catenin pathway by targeting QKIs.

摘要

甲状腺癌是最常见的内分泌肿瘤类型,其发病率正在迅速上升。微小RNA(miR)-574-5p是各类癌症中的一个候选致癌基因。本研究发现,miR-574-5p通过靶向震颤蛋白(QKIs),经由β-连环蛋白/ Wnt信号传导途径影响BCPAP和FTC133甲状腺癌细胞的细胞周期分布和凋亡。MTT试验表明,敲低miR-574-5p可抑制甲状腺癌细胞的增殖。荧光激活细胞分选分析表明,抑制miR-574-5p可诱导细胞的G/S期阻滞和凋亡。逆转录定量聚合酶链反应和蛋白质印迹分析显示,敲低miR-574-5p可显著上调QKIs的mRNA和蛋白质表达水平。此外,蛋白质印迹分析发现,敲低miR-574-5p还可通过下调β-连环蛋白、细胞周期蛋白D1和生存素的表达以及上调β-连环蛋白的磷酸化来抑制Wnt/β-连环蛋白信号通路。进一步敲低QKIs并联合敲低miR-574-5p,不仅增加了β-连环蛋白、细胞周期蛋白D1和生存素的表达,还挽救了因敲低miR-574-5p而诱导的甲状腺癌细胞凋亡。总之,这些发现表明,miR-574-5p的异常上调可能通过靶向QKIs调节Wnt/β-连环蛋白信号通路而具有致癌性。

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