Identification of Gαi1 as a key regulator of tumor progression in nasopharyngeal carcinoma.

PURPOSE: The G protein α inhibitory subunit 1 (Gαi1) has been implicated in cancer progression. This study investigates its role in nasopharyngeal carcinoma (NPC), focusing on its expression, clinical relevance, and molecular mechanisms. METHODS: The expression level and prognostic value of Gαi1 were evaluated based on public databases, and further confirmed in NPC tissues and cells by western blot analysis, quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). Functional assays, including Gαi1 knockdown in NPC cell lines, assessed its effects on proliferation, migration, invasion, apoptosis, and signaling. The Gαi1-SETD7 interaction was explored to elucidate underlying mechanisms. RESULTS: Gαi1 was upregulated in tumor tissues, with the highest expression in head and neck squamous cell carcinoma (HNSCC). Elevated Gαi1 levels correlated with poor prognosis and increased metastasis. In NPC, Gαi1 overexpression was confirmed at both mRNA and protein levels. Gαi1 knockdown reduced cell cycle progression, ERK and Akt-mTOR signaling, inhibited cell proliferation, migration, and invasion, and promoted apoptosis. In vivo, Gαi1 silencing suppressed tumor growth. Moreover, Gαi1 regulated SETD7 expression, with SETD7 overexpression rescuing the effects of Gαi1 knockdown. CONCLUSION: Gαi1 promotes tumor progression in NPC through the cell cycle, ERK and Akt-mTOR pathway and by regulating SETD7. Targeting Gαi1 or its signaling may offer a novel therapeutic strategy for NPC and potentially other cancers.