Spleen tyrosine kinase facilitates the progression of papillary thyroid cancer regulated by the hsa_circ_0006417/miR-377-3p axis

脾脏酪氨酸激酶促进由 hsa_circ_0006417/miR-377-3p 轴调控的乳头状甲状腺癌进展

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作者:Guangmou Tan, Shiyang Zheng, Boxuan Zhou, Zhaohong Mo, Qiong Zhang, Donghui Zhang, Aimin Li, Xinhui Liu

Abstract

Papillary thyroid cancer (PTC) is a prevalent malignancy worldwide. Spleen tyrosine kinase (SYK) is a crucial enzyme that participates in various biological processes, including cancer progression. This study aims to uncover the biological function of SYK in PTC. SYK expression patterns in PTC were evaluated using quantitative real time polymerase chain reaction (qRT-PCR), immunohistochemistry (IHC), and western blot. Cell function assays were performed to assess the effects of SYK on PTC. Bioinformatics analysis was conducted to identify intriguing microRNA (miRNA) and circular RNA (circRNA). Dual-Luciferase Reporter or RNA immunoprecipitation assays were used to investigate the correlation among SYK, miR-377-3p, and hsa_circ_0006417. SYK was upregulated in PTC. Overexpression of SYK exhibited a positive correlation with tumor size, lymph node metastasis, and unfavorable disease-free survival. Functional assays revealed that SYK exerted tumorigenic effect on PTC cells through mTOR/4E-BP1 pathway. Mechanistically, hsa_circ_0006417 and miR-377-3p regulated SYK expression, offering modulating its tumor-promoting effects. Collectively, SYK acts as an oncogene in PTC through mTOR/4E-BP1 pathway, which is regulated by the hsa_circ_0006417/miR-377-3p axis, thereby providing a potential alternative for PTC treatment.

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