REX1 promotes EMT-induced cell metastasis by activating the JAK2/STAT3-signaling pathway by targeting SOCS1 in cervical cancer

Abstract

ZFP42 zinc finger protein (REX1), a pluripotency marker in mouse pluripotent stem cells, has been identified as a tumor suppressor in several human cancers. However, the function of REX1 in cervical cancer remains unknown. Both IHC and western blot assays demonstrated that the expression of REX1 protein in cervical cancer tissue was much higher than that in normal cervical tissue. A xenograft assay showed that REX1 overexpression in SiHa and HeLa cells facilitated distant metastasis but did not significantly affect tumor formation in vivo. In addition, in vitro cell migration and invasion capabilities were also promoted by REX1. Mechanistically, REX1 overexpression induced epithelial-to-mesenchymal transition (EMT) by upregulating VIMENTIN and downregulating E-CADHERIN. Furthermore, the JAK2/STAT3signaling pathway was activated in REX1-overexpressing cells, which also exhibited increased levels of p-STAT3 and p-JAK2, as well as downregulated expression of SOCS1, which is an inhibitor of the JAK2/STAT3-signaling pathway, at both the transcriptional and translational levels. A dual-luciferase reporter assay and qChIP assays confirmed that REX1 transsuppressed the expression of SOCS1 by binding to two specific regions of the SOCS1 promoter. Therefore, all our data suggest that REX1 overexpression could play a crucial role in the metastasis and invasion of cervical cancer by upregulating the activity of the JAK2/STAT3 pathway by trans-suppressing SOCS1 expression.

Resveratrol Suppresses the Growth and Metastatic Potential of Cervical Cancer through Inhibiting STAT3Tyr705 Phosphorylation

“…In the current study, our data showed that treatment with resveratrol, S3I201, or AG490 resulted in (58)(59)(60). We showed that resveratrol and S3I201 or AG490 consistently decreases phosphorylation of STAT3 Tyr705 in Hela cells and SiHa cells.…”

Resveratrol suppresses the growth and metastatic potential of cervical cancer by inhibiting STAT3Tyr705 phosphorylation

“…Studies have demonstrated that the activation of STAT3 signaling promotes metastasis of cervical cancer cells. [60][61][62] S3I201 inhibits STAT3, while AG490 is an inhibitor of the JAK upstream of STAT3. Our study indicated that RES had similar effects to S3I201 and AG490, resveratrol combined with S3I201 or AG490, and consistently decreased phosphorylation levels of STAT3 Tyr705 in HeLa and SiHa cells.…”

SOCS-6 promotes mitochondrial fission and cardiomyocyte apoptosis and is negatively regulated by QKI mediated miR-19b

“…miR-19 has also been found to promote the progression of osteosarcoma by targeting and downregulating SOCS-6 in association with JAK2/STAT3 signaling [36]. The JAK2/STAT3 signaling pathway is involved in the progression of several cancers and is associated with other SOCS proteins through feedback regulation in various cell processes [37][38][39][40]. Although the research on JAK2/STAT3 signaling and mitochondrial fragmentation is limited, one study has proposed that JAK2/STAT3 signaling can prevent myocardial IR injury by reducing IR-induced mitochondrial oxidative damage [41].…”