G3BP2 regulated by the lncRNA LINC01554 facilitates esophageal squamous cell carcinoma metastasis through stabilizing HDGF transcript

Abstract

Metastasis is the leading cause of death of patients with esophageal squamous cell carcinoma (ESCC). Although an increasing number of studies have demonstrated the involvement of G3BP2 in several human cancers, how G3BP2 interacts with long noncoding RNAs and regulates mRNA transcripts in mediating ESCC metastasis remains unclear. In this study, we uncovered that G3BP2 was upregulated in ESCC. Further analysis revealed that upregulation of G3BP2 was significantly correlated with lymph node metastasis, depth of tumor invasion and unfavorable outcomes in ESCC patients. Both in vitro and in vivo functional assays demonstrated that G3BP2 dramatically enhanced ESCC cell migration and invasion. Mechanistically, LINC01554 maintained the high G3BP2 expression in ESCC by protecting G3BP2 from degradation through ubiquitination and the interaction domains within LINC01554 and G3BP2 were identified. In addition, RNA-seq revealed that HDGF was regulated by G3BP2. G3BP2 bound to HDGF mRNA transcript to stabilize its expression. Ectopic expression of HDGF effectively abolished the G3BP2 depletion-mediated inhibitory effect on tumor cell migration. Intriguingly, introduction of compound C108 which can inhibit G3BP2 remarkedly suppressed ESCC cell metastasis in vitro and in vivo. Collectively, this study describes a newly discovered regulatory axis, LINC01554/G3BP2/HDGF, that facilitates ESCC metastasis and will provide novel therapeutic strategies for ESCC.

Potential Effects of Metformin on the Vitality, Invasion, and Migration of Human Vascular Smooth Muscle Cells via Downregulating lncRNA-ATB

“…In our research, we find that ATB could directly bind to p53 and thus regulate the expression level. In a recent study, LINC01554 maintained the high G3BP2 expression in ESCC by protecting G3BP2 from degradation through ubiquitination also edified us the mechanism that lncRNA could bind to target gene and regulate that [ 29 ]. In addition, metformin induction remarkably upregulated p53 in VSMCs.…”

Epigenetic modifications in esophageal cancer: An evolving biomarker

“…The lncRNA MIR22HG has also been suggested as a novel cancer prognostic biomarker acting through ceRNA ( Zhang C et al, 2020 ). Similarly, the lncRNAs NORAD, AGPG, DNM3OS, VESTAR, IRF1-AS and LINC01554 have strong potential for application in the diagnosis and treatment of esophageal cancer ( Zhang B. X et al, 2019 ; Huang et al, 2019 ; Liu Y et al, 2020 ; Wang Y et al, 2021 ; Jia et al, 2021 ; Zheng et al, 2022 ) ( Figure 1 ; Table 2 ).…”

LncRNA RPL34-AS1 suppresses the proliferation, migration and invasion of esophageal squamous cell carcinoma via targeting miR-575/ACAA2 axis

“…EMT-related lncRNA DDX11-AS1 facilitated ESCC process through targeting miR-30d-5p to regulate SNAI1/ZEB2 expression and Wnt/beta-catenin pathway [ 12 ]. LncRNA LINC01554 acted as a promoter of ESCC through regulating G3BP2/HDGF axis to enhance ESCC cell migration and invasion [ 13 ]. In brief, these studies confirmed that lncRNAs served as clinical therapeutic targets for human ESCC.…”