STYXL1 promotes malignant progression of hepatocellular carcinoma via downregulating CELF2 through the PI3K/Akt pathway.

Abstract

This study was aimed to investigate the expression characteristics of STYXL1 in hepatocellular carcinoma (HCC), and to further analyze its regulatory role in promoting HCC development by targeting CELF2 to activate the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway. Expression levels of STYXL1 in 25 pairs of HCC tissue specimens and paracancerous normal ones collected from HCC patients were examined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Meanwhile, qRT-PCR was also performed to further verify the expression of STYXL1 in HCC cell lines. In addition, after STYXL1 knockdown model was constructed by lentivirus transfection in HCC cell lines Hep3B and Huh7, the Cell Counting Kit-8 (CCK-8), cell colony formation, 5-Ethynyl-2'-deoxyuridine (EdU), and flow cytometry assays were performed to analyze the influence of STYXL1 on HCC cell functions. Furthermore, an in-depth study of the relationship between STYXL1 and CELF2 was conducted to figure out the underlying mechanism. The results of qRT-PCR revealed that the expression level of STYXL1 in HCC samples was remarkably higher than that in adjacent ones, and the difference was statistically significant. Compared with HCC patients with low expression of STYXL1, patients with high expression of STYXL1 had a higher overall survival rate. Similarly, the proliferation ability of HCC cells in sh-STYXL1 group remarkably decreased compared with controls, while the apoptosis ability was oppositely enhanced. In addition, Western Blotting results indicated that STYXL1 could elevate the expressions of PI3K/Akt pathway-related proteins. Meanwhile, a negative correlation between CELF2 and STYXL1 was identified in HCC tissues. Finally, the result of cell reverse experiments demonstrated that STYXL1 could affect the malignant progression of HCC via modulating CELF2 expression. STYXL1 expression was remarkably upregulated in HCC tissues, as well as in cell lines. Its level was closely related to the poor prognosis of HCC patients. In addition, STYXL1 might be able to accelerate HCC proliferation rate and inhibit cell apoptosis via downregulating CELF2 through the PI3K/Akt pathway.