JARID2 promotes invasion and metastasis of hepatocellular carcinoma by facilitating epithelial-mesenchymal transition through PTEN/AKT signaling

Abstract

JARID2 is crucial for maintenance of pluripotency and differentiation of embryonic stem cells. However, little is known about the role of JARID2 in metastasis of hepatocellular carcinoma (HCC). This study found that JARID2 expression was significantly higher in HCC tissues than that in adjacent non-tumor liver tissues (ANLTs), and its expression level correlated with HCC metastasis. High JARID2 expression was significantly correlated with multiple tumor nodules, high Edmondson-Steiner grade, microvascular invasion, advanced TNM stage and advanced BCLC stage (all P < 0.05) and indicated poor prognosis of HCC in training and validation cohorts (all P < 0.05) totaling 182 patients. High JARID2 expression was an independent and significant risk factor for disease-free survival (DFS; P = 0.017) and overall survival (OS; P = 0.041) after curative liver resection in training cohort, and also validated as an independent and significant risk factor for DFS (P = 0.033) and OS (P = 0.031) in validation cohort. Moreover, down-regulation of JARID2 dramatically inhibited HCC cell migration, invasion, proliferation in vitro and metastasis in vivo, whereas overexpression of JARID2 significantly increased migration, invasion, proliferation in vitro and metastasis in vivo. Mechanistically, the data showed that JARID2 exerted its function by repressing PTEN expression through increasing H3K27 trimethylation (H3K27me3) at PTEN promoter region, which subsequently resulted in activation of protein kinase B (AKT) and enhanced epithelial-mesenchymal transition (EMT). In conclusion, this study revealed that JARID2 promotes invasion and metastasis of HCC by facilitating EMT through PTEN/AKT signaling.

Knockdown of JARID2 inhibits the viability and migration of placenta trophoblast cells in preeclampsia

“…Previous studies have demonstrated that deficient migration and shallow invasion of trophoblasts may lead to preeclampsia (16,17). JARID2 has been suggested to regulate tumor cell migration and invasion; a previous study revealed that knockdown of JARID2 markedly inhibits hepatocellular carcinoma cell migration and invasion (13). Consistent with the results of this previous study, in the present study, it was observed that the knockdown of JARID2 significantly inhibited the viability and migration/invasion of HTR8/SVneo cells.…”

“…Therefore, the suppression of PI3K/Akt signaling may be a promising approach for treating preeclampsia. A recent study reported that JARID2 promotes the activation of Akt in hepatocellular carcinoma (13). In the present study, it was observed that the knockdown of JARID2 suppressed the levels of phosphorylated PI3K and Akt in HTR8/SVneo cells.…”

“…It has previously been observed that JARID2 is involved in the development and progression of a number of types of tumor such as lung and colon cancer (11,12). Recently, Lei et al (13) reported that downregulation of JARID2 inhibits hepatocellular carcinoma cell migration, invasion and proliferation in vitro, and metastasis in vivo. However, little is known about the role of JARID2 in the metastasis of placenta trophoblast cells.…”

Galectin-1 Promotes Metastasis in Gastric Cancer Through a Sphingosine-1-Phosphate Receptor 1-Dependent Mechanism

“…The phenomenon known as epithelial-mesenchymal transition (EMT) promotes invasion and metastasis in many cancers [29][30][31], and we hypothesized that S1PR1 might be involved in EMT of GC cells. We treated MGC-803 cells with 10 ng/ml TGF-β1 for 24 hours.…”

Integrative Clustering Reveals a Novel Subtype of Soft Tissue Sarcoma With Poor Prognosis

“…The encoded protein is a DNA-binding protein that functions as a transcriptional repressor. It was reported to promote the invasion and metastasis of hepatocellular carcinoma by facilitating epithelialmesenchymal transition through the PTEN/AKT signaling pathways (Lei et al, 2016) and is essential for the maintenance of tumor-initiating cells in bladder cancer (Zhu et al, 2017). The protein encoded by CDK6 is a member of the CMGC family of serine/threonine protein kinases.…”