AEG‐1 induces gastric cancer metastasis by upregulation of eIF4E expression

Abstract

Gastric cancer is the third leading cause of cancer‐related deaths worldwide, and patients with lymph node, peritoneal and distant metastasis have a poor prognosis. Overexpression of Astrocyte‐elevated gene‐1 (AEG‐1) has been reported to be correlated with the progression and metastasis of gastric cancer. However, its mechanisms are quite unclear. In this study, we found that elevated expression of AEG‐1 was correlated with metastasis in human gastric cancer tissues. Moreover, gain‐ or loss‐of‐function of AEG‐1, respectively, promoted or suppressed epithelial–mesenchymal transition (EMT), migration and invasion of gastric cancer cells. AEG‐1 positively regulated eIF4E, MMP‐9 and Twist expression. Manipulating eIF4E expression by transfection of overexpression constructs or siRNAs partially eliminated AEG‐1‐regulated EMT, cell migration and invasion. In addition, overexpression or knockdown of eIF4E promoted or suppressed EMT, cell migration and invasion in parallel with upregulation of MMP‐9 and Twist expression, while manipulating eIF4E expression partially abrogated AEG‐1‐induced MMP‐9 and Twist. Finally, silencing of AEG‐1 expression not only inhibited tumour growth in parallel with downregulation of eIF4E, MMP‐9 and Twist expression in a xenograft nude mouse model, but also suppressed lymph node and peritoneal metastasis of gastric cancer in an orthotopic nude mouse model. These findings suggest that AEG‐1 promotes gastric cancer metastasis through upregulation of eIF4E‐mediated MMP‐9 and Twist, which provides new diagnostic markers and therapeutic targets for cancer metastasis.

<p>Long Noncoding RNA DLGAP1-AS1 Promotes the Aggressive Behavior of Gastric Cancer by Acting as a ceRNA for microRNA-628-5p and Raising Astrocyte Elevated Gene 1 Expression</p>

“…[28][29][30] Functionally, AEG-1 performes cancer-promoting actions in gastric carcinogenesis and cancer progression, and is involved in multiple aggressive phenotype. [31][32][33][34][35] Yet, as far as we know, there has been no study that has explored the issue of DLGAP1-AS1, miR-628-5p, and AEG-1 in GC. Herein, we also attempted to address the functions and associations between DLGAP1-AS1, miR-628-5p, and AEG-1 in GC.…”

Metastasis-associated protein 2 (MTA2) promotes the metastasis of esophageal squamous cell carcinoma via EIF4E-Twist feedback loop

“…On the contrary, the expression level of Twist was signi cantly increased in the EIF4E-overexpressing cells (Fig. 8H), which was consistent with previous report [26]. Collectively, these results indicated that MTA2 and EIF4E-Twist formed a positive feedback to regulate the development of ESCC.…”

“…In present study, our data also indicated that the expression of Twist was suppressed when EIF4E was silenced, while EIF4E overexpression increased the Twist level. According to the previous report [26], activation of EIF4E promotes metastatic progression via translation of several EMT-associated mRNAs such as Twist. EIF4E binds to the 5′7-methylguanosine cap of mRNAs and recruits to the EIF4F complex (EIF4G, EIF4A and EIF4E ), expanding mRNA second structure to expose the translation initiation codon and enabling translation [41].…”

Effect of verbascoside on apoptosis and metastasis in human oral squamous cell carcinoma

“…After a 24‐hr incubation period, a cotton swab was used to wipe and remove the cells from the upper chamber. Cells that migrated or passed through the filter were fixed with 100% ethanol and then stained for 30 min with 0.1% crystal violet . Cells were observed with a light microscope and counted in five randomly selected fields.…”

“…Cells that migrated or passed through the filter were fixed with 100% ethanol and then stained for 30 min with 0.1% crystal violet. 17 Cells were observed with a light microscope and counted in five randomly selected fields. The average number of cells in each field was then calculated.…”