Histol Histopathol, Vol 39, Sun et al.

GNA15 facilitates the malignant development of thyroid carcinoma cells via the BTK-mediated MAPK signaling pathway

Yihan Sun and Yifan Han

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

Corresponding Author: Yifan Han, Neck Surgery Department, The 2nd School of Medicine, WMU/The 2nd Affiliated Hospital and Yuying Children’s Hospital of WMU, No. 1111, East Section of Wenzhou Avenue, Longwan District, Wenzhou City, Zhejiang Province, 325000, China. e-mail: hanyif_yifan@163.com

Summary. 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. Histol Histopathol

Key words: Thyroid carcinoma, G protein subunit alpha 15, Bruton tyrosine kinase, MAPK signaling pathway, Malignant phenotype

DOI: 10.14670/HH-18-714