STAT3 promotes the proliferation and migration of hepatocellular carcinoma cells by regulating AKT2

Abstract

Abstract. The aim of the present study was to investigate the correlation of STAT3 and AKT in HCC cells. HCC cells were transfected with si-STAT3 and si-AKT2 in vitro and the mRNA expression of STAT3 and AKT was detected by RT-PCR, and the protein expression was measured by western blot. MTT assays were used to evaluate cell proliferation, and Transwell assays were performed to detect the ability of migration and invasion. The relationship between STAT3 and AKT was analyzed by ChIP and Dual-luciferase reporter (DLR) assays. A nude mice experiment was used to verify the correlation. In the present study, we found that the expression of p-AKT2 and its downstream molecules were reduced in HCC cells transfected with si-STAT3, and the expression of p-STAT3 and its downstream molecules was decreased in HCC cells transfected with si-AKT2. Moreover, the ability of HCC cells proliferation, migration and invasion was decreased in si-STAT3 transfection group, but AKT2 reversed the role of si-STAT3 in HCC cells. The ChIP experiment found that STAT3 could bind to the AKT2 promoter in HCC cells. The DLR assay showed that the luciferase activity of AKT2 promoter was enhanced in HCC cells treated by IL-6. The nude mice experiment found that the tumor grew slowly after transfection with the STAT3-siRNA lentiviral vector, while AKT2 reversed the effect. STAT3 and AKT2 had mutual regulatory relationship, and STAT3 promoted the occurrence and development of HCC by regulating AKT2.

JAK/STAT signaling in hepatocellular carcinoma

“…Zhang and colleagues demonstrated that STAT3 performs this function by regulating the expression of AKT2 [65]. HCC cells transfected with STAT3-specific small interfering RNAs (siRNAs) induced a downregulation of AKT2 expression along with its target genes, leading to a significant reduction in the invasive properties of the cells in vitro [65]. The direct crosstalk between the JAK/STAT and PI3K/Akt2 pathway further supports the role of STAT3 in promoting invasion and metastasis in HCC.…”

“…Furthermore, STAT3 may promote the invasiveness of HCC by regulating alternative oncogenic pathways involved in metastasis. One such pathway is the PI3K/Akt2 signaling pathway, which modulates cell adhesion and invasion both in vitro and in vivo [64,65]. Zhang and colleagues demonstrated that STAT3 performs this function by regulating the expression of AKT2 [65].…”

“…One such pathway is the PI3K/Akt2 signaling pathway, which modulates cell adhesion and invasion both in vitro and in vivo [64,65]. Zhang and colleagues demonstrated that STAT3 performs this function by regulating the expression of AKT2 [65]. HCC cells transfected with STAT3-specific small interfering RNAs (siRNAs) induced a downregulation of AKT2 expression along with its target genes, leading to a significant reduction in the invasive properties of the cells in vitro [65].…”

Modulating the Crosstalk between the Tumor and Its Microenvironment Using RNA Interference: A Treatment Strategy for Hepatocellular Carcinoma

“…When HCC cell lines (SMMC7721 and QGY-7703) were transfected with siRNA targeting STAT3 and AKT2, a significant decrease in the mRNA level of AKT2 and STAT3 was observed. Furthermore, nude mice were used to verify the correlation, and a decreased ability for HCC cell proliferation, migration and invasion has been since concluded [ 119 ].…”

Characterization of Stanniocalcin-1 Expression in Macrophage Differentiation

“…The high expression of TBC1D3 was associated with decreased STAT3 phosphorylation in recipient cells(Qin et al 2019). A decreased phosphorylated level of STAT3 was found to inhibit the proliferation and migration of HCC(Xie et al 2018). Consistently in this study, the incubation of Hep3B cells in conditioned media of siRNA STC1 -transfected M1-polarized cells showed a significant reduction in cell motility.…”