Neck Surgery Department, The 2nd School of Medicine, WMU/The 2nd Affiliated Hospital and Yuying Children's Hospital of WMU, Longwan District, Wenzhou City, Zhejiang Province, China.
Histol Histopathol. 2024 Sep;39(9):1217-1227. doi: 10.14670/HH-18-714. Epub 2024 Jan 19.
G protein subunit alpha 15 (GNA15) is recognized as an oncogene for some cancers, however, its role in thyroid carcinoma (TC) is elusive and is investigated in this study. Concretely, bioinformatics was employed to analyze the GNA15 expression profile in TC. The effect of GNA15 on TC cell functions was examined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, and Transwell assays. Expressions of extracellular regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 were determined using Western blot. The involvement of Bruton tyrosine kinase (BTK) in the mechanism of GNA15 was investigated by BTK knockdown and rescue assay. GNA15 presented an overexpression pattern in TC samples, which facilitated the viability, proliferation, migration, and invasion of TC cells; GNA15 silencing led to converse results. Ratios of p-ERK/ERK, p-JNK/JNK, and p-p38/p38 were upregulated by GNA15 overexpression. The BTK deficiency weakened the aforementioned behaviors of TC cells and blocked the MAPK signaling pathway, however, these effects were counteracted by GNA15 overexpression. Collectively, GNA15 contributes to the malignant development of TC cells by binding to BTK and thus activating the MAPK signaling pathway.
G 蛋白亚单位 alpha 15(GNA15)被认为是一些癌症的癌基因,但它在甲状腺癌(TC)中的作用尚不清楚,本研究对此进行了探讨。具体而言,采用生物信息学方法分析 TC 中 GNA15 的表达谱。通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)、集落形成和 Transwell 测定来检测 GNA15 对 TC 细胞功能的影响。采用 Western blot 测定细胞外调节蛋白激酶(ERK)、c-Jun N-末端激酶(JNK)和 p38 的表达。通过 BTK 敲低和挽救实验研究了 Bruton 酪氨酸激酶(BTK)在 GNA15 机制中的作用。GNA15 在 TC 样本中表现出过表达模式,促进了 TC 细胞的活力、增殖、迁移和侵袭;GNA15 沉默导致相反的结果。GNA15 过表达上调了 p-ERK/ERK、p-JNK/JNK 和 p-p38/p38 的比值。BTK 缺乏减弱了 TC 细胞的上述行为,并阻断了 MAPK 信号通路,但 GNA15 过表达逆转了这些作用。总之,GNA15 通过与 BTK 结合并激活 MAPK 信号通路,促进 TC 细胞的恶性发展。