Full
Outline
To investigate the mechanism by which SLC38A1 promotes hepatocellular carcinoma (HCC) progression through glutamine transport-mediated activation of the PI3K/AKT signaling pathway.
Bioinformatics analysis was employed to assess the correlation between SLC38A1 expression and clinicopathological features/prognosis in HCC patients, with functional enrichment analysis of SLC38A1 conducted. SLC38A1 was silenced or over expressed via transfection in Huh-7 cells, with glutamine inhibited using DRP-104 and the PI3K/AKT pathway suppressed using LY294002. Cell viability, proliferation, migration, invasion, and glutamine concentration were evaluated using CCK-8, EdU staining, scratch wound healing assay, Transwell chamber assay, and glutamine assay kits, respectively. PI3K/AKT pathway activity was assessed by Western blotting.
SLC38A1 mRNA and protein levels were significantly higher in HCC tumor tissues than in adjacent normal tissues (P<0.05). HCC patients with high SLC38A1 expression exhibited significantly lower overall survival than those with low expression (P<0.05). SLC38A1 expression correlated significantly with pathologic T-stage (pT), N-stage (pN), M-stage (pM), survival status, and immune infiltration in HCC patients (P<0.05). SLC38A1 silencing markedly reduced glutamine uptake in HCC cells (P<0.001), suppressing cell viability, proliferation, migration, invasion, and PI3K/AKT pathway activity (P<0.001). Conversely, SLC38A1 overexpression promoted proliferation, migration, invasion, and PI3K/AKT activation (P<0.001). DRP-104-mediated glutamine inhibition suppressed HCC cell malignancy and PI3K/AKT signaling while abolishing the oncogenic effects of SLC38A1 overexpression (P<0.001). PI3K/AKT pathway inhibition blocked the pro-tumorigenic effects of SLC38A1 overexpression (P<0.001).
SLC38A1 promotes proliferation, migration, and invasion in HCC by activating the PI3K/AKT pathway through enhanced glutamine transport.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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