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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

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Abstract

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.

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Funding

This work was supported by the National Natural Science Foundation of China (81572916).

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  1. Haili Tang and Ping Yang have contributed equally to this work.

Authors and Affiliations

  1. Department of General Surgery, Tangdu Hospital Fourth Military Medical University, 569 Xinsi Road, Xi’an, 710032, China

    Haili Tang, Ping Yang, Xiaojun Yang, Shujia Peng, Xi’e Hu & Guoqiang Bao

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  1. Haili Tang
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  2. Ping Yang
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  3. Xiaojun Yang
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Correspondence to Guoqiang Bao.

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This study was conducted in the laboratory of Tangdu Hospital Fourth Military Medical University. The human specimens used for treatment and protocol employed were approved by the Ethical Committee of Tangdu Hospital Fourth Military Medical University. The experimental procedures have been carried out in accordance with the ethical standards as of Declaration of Helsinki.

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Tang, H., Yang, P., Yang, X. et al. Growth factor receptor bound protein-7 regulates proliferation, cell cycle, and mitochondrial apoptosis of thyroid cancer cells via MAPK/ERK signaling. Mol Cell Biochem 472, 209–218 (2020). https://doi.org/10.1007/s11010-020-03798-4

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  • DOI: https://doi.org/10.1007/s11010-020-03798-4

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