STC2 knockdown inhibits cell proliferation and glycolysis in hepatocellular carcinoma through promoting autophagy by PI3K/Akt/mTOR pathway

The pathogenesis exploration and timely intervention of hepatocellular carcinoma (HCC) are crucial due to its global impact on human health . As a general tumor biomarker, stanniocalcin 2 (STC2), its role in HCC remains unclear. We aimed to analyze the effect and mechanism of STC2 on HCC. STC2 expressions in HCC tissues and cell lines were measured. si-STC2 and oe-STC2 transfections were utilized to analyze how STC2 affected cell functions. Functional enrichment analysis of STC2 was performed by Gene Set Enrichment Analysis (GSEA). The regulatory mechanism of STC2 on HCC was investigated using 2-DG, 3-MA, IGF-1, Rap, and LY294002 . The impact of STC2 on HCC progression in vivo was evaluated by the tumor formation experiment. Higher levels of STC2 expression were observed in HCC tissues and cell lines. Besides, STC2 knockdown reduced proliferation, migration, and invasion, while inducing cell apoptosis . Further analysis indicated a positive correlation between STC2 and glycolysis. STC2 knockdown inhibited glycolysis progression and down-regulated the expressions of PKM2 , GLUT1, and HK2 in HCC cells . However, treatment with glycolysis inhibitor (2-DG) prevented oe-STC2 from promoting the growth of HCC cells. Additionally, STC2 knockdown up-regulated the levels of LC3II/LC3I and Beclin1 and reduced the phosphorylation of PI3K, AKT, and mTOR . Treatment with 3-MA, IGF-1, Rap, and LY294002 altered the function of STC2 on proliferation and glycolysis in HCC cells. Tumor formation experiment results revealed that STC2 knockdown inhibited HCC progression. STC2 knockdown inhibited cell proliferation and glycolysis in HCC through the PI3K/Akt/mTOR pathway-mediated autophagy induction. This study proposes that STC2 is a potential therapeutic target and prognostic marker for HCC. Mechanistically, STC2 inhibits autophagy and enhances glycolysis by activating the PI3K/Akt/mTOR pathway, thereby promoting malignant behaviors such as proliferation, migration, and invasion of HCC cells. • Upregulation of STC2 expression in HCC tissues and cells indicated a poor prognosis. • Knockdown of STC2 inhibited proliferation and glycolysis of HCC cells. • The PI3K/Akt/mTOR pathway participated in HCC progression by regulating autophagy. • Knockdown of STC2 inhibited HCC through PI3K/Akt/mTOR pathway-mediated autophagy. • This work will enrich insights into the pathogenesis and potential therapy of HCC.