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Updated: Jul 4, 2025

Induction and Analysis of Epithelial to Mesenchymal Transition
Published on: August 27, 2013
GNA15 facilitates the malignant development of thyroid carcinoma cells via the BTK-mediated MAPK signaling pathway
1Neck 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.
Abstract:
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.
Insights
G protein subunit alpha 15 (GNA15) promotes thyroid carcinoma (TC) progression by activating the MAPK pathway via Bruton tyrosine kinase (BTK). Silencing GNA15 inhibits TC cell viability, proliferation, migration, and invasion.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- G protein subunit alpha 15 (GNA15) is implicated as an oncogene in various cancers.
- The specific role of GNA15 in thyroid carcinoma (TC) remains largely uncharacterized.
Purpose of the Study:
- To investigate the expression and function of GNA15 in thyroid carcinoma.
- To elucidate the underlying molecular mechanisms, including its interaction with Bruton tyrosine kinase (BTK) and the MAPK signaling pathway.
Main Methods:
- Bioinformatic analysis of GNA15 expression in TC.
- In vitro assays (MTT, colony formation, Transwell) to assess TC cell functions.
- Western blot analysis for MAPK pathway components (ERK, JNK, p38).
- BTK knockdown and rescue experiments to determine GNA15's mechanism.
Main Results:
- GNA15 was significantly overexpressed in TC tissues.
- GNA15 overexpression enhanced TC cell viability, proliferation, migration, and invasion.
- GNA15 upregulated the phosphorylation of ERK, JNK, and p38, indicating MAPK pathway activation.
- BTK deficiency inhibited TC cell malignant behaviors and MAPK signaling, but these effects were reversed by GNA15 overexpression.
Conclusions:
- GNA15 acts as an oncogene in thyroid carcinoma.
- GNA15 promotes TC cell malignancy by interacting with BTK and activating the MAPK signaling pathway.
- Targeting GNA15 may represent a potential therapeutic strategy for thyroid carcinoma.
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