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.

中文翻译：

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胰高血糖素受体的肿瘤促进作用：通过调节EMT和P38 / ERK途径，成为甲状腺乳头状癌的有前途的生物标志物。

胰高血糖素是参与维持葡萄糖稳态的关键激素。近年来，为确定胰高血糖素受体（GCGR）的作用做出了巨大努力，但有关其功能和机制仍不完善。我们进行了这项研究，以验证其对甲状腺乳头状癌（PTC）进展的潜在影响。使用癌症基因组图谱（TCGA）数据库阐述了GCGR表达与PTC之间的相关性。Kaplan–Meier方法用于分析GCGR表达与PTC患者预后之间的联系。通过定量实时聚合酶链反应（qRT-PCR）和western印迹分析测量GCGR表达。同时，按照siRNA策略使用细胞增殖和集落形成分析法阐明了细胞活力。进行Transwell分析以测量PTC细胞的侵袭和迁移。进行流式细胞术分析以检查细胞凋亡能力。使用cAMP ELISA试剂盒测量PTC细胞中的cAMP水平。我们的数据确定，与正常组织和Nthy-ori 3-1相比，PTC组织和细胞中GCGR的表达水平增加了。PTC患者中GCGR表达上调与生存率降低相关。体外功能分析表明，GCGR抑制可减弱PTC细胞的增殖，集落形成，侵袭和迁移，同时增强细胞凋亡。下调的GCGR能够提高cAMP水平。此外，GCGR降低可能导致上皮-间质转化（EMT）和P38 / ERK途径失活。结论，