Mechanistic study on the regulation of hepatocellular carcinoma progression by GNAI2 possibly through the PI3K/AKT pathway

Hepatocellular carcinoma (HCC), the most common form of liver cancer, remains poorly understood in terms of its underlying mechanisms. The protein GNAI2 has been shown to regulate the transcription of multiple biomolecules and is thought to contribute to the onset and progression of several cancers. This study aimed to uncover how GNAI2 influences HCC development at the molecular level. To explore the expression patterns and prognostic significance of GNAI2, various resources including TIMER2.0, TCGA, GEO, and HPA were employed. The examination of clinical data from TCGA enabled the investigation of the relationships between GNAI2 levels and the clinical-pathological characteristics of HCC patients. The functional roles of GNAI2 in HCC were characterized using GO and KEGG analyses. Furthermore, the influence of GNAI2 expression on immune cell infiltration was evaluated utilizing the TISIDB and TIMER2.0 databases. Concurrently, single-cell RNA sequencing data sourced from the TISCH2 database offered valuable insights into the expression of GNAI2 within immune cells. Investigations into the role of GNAI2 in modulating drug responsiveness in HCC were also undertaken. Experimental validations were conducted to ascertain the biological roles and molecular mechanisms of GNAI2 in HCC. The findings indicate that GNAI2 is consistently upregulated in HCC tissues. Survival analysis pointed to a connection between higher GNAI2 levels and shorter overall survival in HCC patients, hinting at its possible use as a diagnostic indicator. GNAI2 expression was notably associated with T staging. Functional enrichment of GNAI2-related genes suggested that GNAI2 may drive HCC progression through the PI3K/AKT signaling pathway. Moreover, GNAI2 appeared to have a clear impact on immune infiltration within tumors, especially on M2 macrophages. Drug sensitivity analysis indicated a link between many of the tested drugs and PI3K/AKT inhibitors. Knocking down GNAI2 in HCCLM3 and MHCC97L cells led to reduced cell migration, proliferation, and invasion, increased apoptosis, and lower phosphorylation levels in the PI3K/AKT pathway. Taken together, these findings suggest that GNAI2 could serve as a useful biomarker for HCC diagnosis and prognosis. Silencing GNAI2 noticeably weakened the ability of HCC cells to grow, move, and invade, likely by modulating the PI3K/AKT signaling axis.