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Growth factor receptor bound protein-7 regulates proliferation, cell cycle, and mitochondrial apoptosis of thyroid cancer cells via MAPK/ERK signaling.
Molecular and Cellular Biochemistry ( IF 3.5 ) Pub Date : 2020-06-23 , DOI: 10.1007/s11010-020-03798-4
Haili Tang 1 , Ping Yang 1 , Xiaojun Yang 1 , Shujia Peng 1 , Xi'e Hu 1 , Guoqiang Bao 1
Affiliation  

It is of great significance to explore the molecular mechanism of thyroid cancer (TC) pathogenesis for its improvement and therapy. Growth factor receptor bound protein-7 (GRB7) has been regarded as an important regulatory gene in the developments of various malignant tumors. Our study aimed to illustrate the role of GRB7 in the TC pathology mechanism. Firstly, GRB7 was found to be significantly upregulated in 49 cases of TC tissues and 5 TC cell lines by using real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting. Silencing GRB7 with siRNA dramatically inhibited proliferation and induced cell cycle arrest in TC cells. Besides, GRB7 silence resulted in the decrease of adenosine triphosphate content, glucose uptake, and lactose production in TC cells and attenuated the activity and expression of mitochondrial respiratory complex. We also demonstrated that GRB7 downregulation increased the levels of Bax and caspase 3, and inhibited the expression of Bcl-2, suggesting the induced mitochondrial apoptosis. More importantly, our study proved that mitogen-activated protein kinase/extracellular-regulated protein kinases (MAPK/ERK) signaling played a crucial role in the regulation of GRB7 on TC cell functions. In general, the present research verified that GRB7 was upregulated during TC development and modulated the proliferation, cell cycle, and mitochondrial apoptosis of TC cells by activating MAPK/ERK pathway. This may provide a novel target for the therapeutic strategy of TC.



中文翻译:


生长因子受体结合蛋白 7 通过 MAPK/ERK 信号传导调节甲状腺癌细胞的增殖、细胞周期和线粒体凋亡。



探讨甲状腺癌(TC)发病的分子机制对于改善和治疗甲状腺癌具有重要意义。生长因子受体结合蛋白7(GRB7)被认为是多种恶性肿瘤发生发展的重要调控基因。我们的研究旨在阐明 GRB7 在 TC 病理机制中的作用。首先,通过实时定量聚合酶链反应(RT-qPCR)和蛋白质印迹发现GRB7在49例TC组织和5个TC细胞系中显着上调。用 siRNA 沉默 GRB7 可显着抑制 TC 细胞的增殖并诱导细胞周期停滞。此外,GRB7沉默导致TC细胞中三磷酸腺苷含量、葡萄糖摄取和乳糖产生减少,并减弱线粒体呼吸复合物的活性和表达。我们还证明,GRB7 下调会增加 Bax 和 caspase 3 的水平,并抑制 Bcl-2 的表达,表明诱导线粒体凋亡。更重要的是,我们的研究证明丝裂原激活蛋白激酶/细胞外调节蛋白激酶(MAPK/ERK)信号在GRB7对TC细胞功能的调节中发挥着至关重要的作用。总的来说,本研究证实GRB7在TC发育过程中上调,并通过激活MAPK/ERK通路调节TC细胞的增殖、细胞周期和线粒体凋亡。这可能为TC的治疗策略提供新的靶点。

更新日期:2020-06-24
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