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Tumor promoting effects of glucagon receptor: a promising biomarker of papillary thyroid carcinoma via regulating EMT and P38/ERK pathways

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Abstract

Glucagon is a crucial hormone involved in the maintenance of glucose homeostasis. Large efforts to define the role of glucagon receptor (GCGR) have been continuously made in recent years, but it is still incomplete about its function and mechanism. We performed this study to verify its potential impacts on papillary thyroid carcinoma (PTC) progression. Correlation between GCGR expression and PTC was elaborated using The Cancer Genome Atlas (TCGA) database. The Kaplan–Meier method was used to analyze the connection between GCGR expression and prognosis of PTC patients. GCGR expression was measured by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analysis; simultaneously, cell viability was elucidated using cell proliferation and colony formation assays following siRNAs strategy. Transwell analyses were conducted to measure the invasion and migration of PTC cells. Flow cytometry analysis was conducted to examine apoptotic ability. The cAMP ELISA kit was employed to measure the cAMP level in PTC cells. Our data determined that the expression level of GCGR was increased in PTC tissues and cells in contrast to normal tissues and Nthy-ori 3-1, respectively. Up-regulated GCGR expression was linked with the lower survival rate in patients with PTC. Functional analysis in vitro suggested that GCGR knockdown attenuated PTC cell proliferation, colony formation, invasion, and migration whilst intensified apoptosis. Down-regulated GCGR was able to increase cAMP level. Furthermore, reduction of GCGR could result in the inactivation of epithelial–mesenchymal transition (EMT) and P38/ERK pathways. In conclusion, the findings of this study disclosed that GCGR promoted PTC cell behaviors by mediating the EMT and P38/ERK pathways, serving as a potential diagnostic and prognostic biomarker as well as therapeutic target for PTC.

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Authors and Affiliations

  1. Eye 3 Division of Red Flag Hospital of Mudanjiang Medical University, Mudanjiang, 157000, Heilongjiang, People’s Republic of China

    Hong-Chun Jiang

  2. Color Doppler Ultrasound Room, The Second Affiliated Hospital of Mudanjiang Medical University, Mudanjiang, 157000, Heilongjiang, People’s Republic of China

    Xiang-Ru Chen

  3. Department of Endocrinology, The Second Affiliated Hospital of Mudanjiang Medical University, Mudanjiang, 157000, Heilongjiang, People’s Republic of China

    Hai-Feng Sun

  4. Hepatobiliary Surgery, The Second Affiliated Hospital of Mudanjiang Medical University, Mudanjiang, 157000, Heilongjiang, People’s Republic of China

    Yuan-Wen Nie

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Jiang, HC., Chen, XR., Sun, HF. et al. Tumor promoting effects of glucagon receptor: a promising biomarker of papillary thyroid carcinoma via regulating EMT and P38/ERK pathways. Human Cell 33, 175–184 (2020). https://doi.org/10.1007/s13577-019-00284-y

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