Abstract
Tripartite Motif Containing 25 (TRIM25), a member of TRIM proteins, has been found abnormally expressed in cancers of female reproductive system. Here, TRIM25 was conspicuously expressed in human gastric cancer (GC) tissues in which its higher expression generally correlated with the poor prognosis of patients. Small interfering RNA (siRNA)-mediated knockdown of TRIM25 expression in MGC-803 and AGS cells had no effects on cell proliferation, whereas reduced cell migration and invasion. Gene set enrichment analysis on The Cancer Genome Atlas stomach adenocarcinoma (STAD) dataset revealed that several signaling pathways, including the migration, E-cadherin and transforming growth factor-β (TGF-β) pathways, were enriched in TRIM25 higher expression patients. Moreover, ectopic expression of TRIM25 in a GC cell line with lower expression of TRIM25 significantly promoted the migration and invasion. Further experiments with TGF-β inhibitor suggested that TRIM25 may exert its function through TGF-β pathway. In summary, our results indicate that TRIM25 acts as an oncogene in GC and thus presents a novel target for the detection and treatment of GC.
Highlights
Gastric cancer (GC) ranks the fourth most frequent diagnosed malignant disease and a leading cause of cancer death[1]
Given the fact that several members of TRIM proteins were upregulated in gastric cancer (GC), we re-analyzed RNA-seq data downloaded from The Cancer Genome Atlas website (TCGA) stomach adenocarcinoma (STAD) dataset and found that the Tripartite Motif Containing 25 (TRIM25) level was higher in GC tissues
The survival time was significantly longer in patients with TRIM25-low expression than that in patients with TRIM25-high expression (P < 0.05). These results revealed that TRIM25 expression was up-regulated in GC tissues, which was closely related with poor overall survival of GC patients
Summary
Gastric cancer (GC) ranks the fourth most frequent diagnosed malignant disease and a leading cause of cancer death[1]. TRIM25 has been found to be abnormally expressed in cancers of the female reproductive system. It was reported that TRIM25 was overexpressed in breast cancer[5,6] and ovarian cancer[7]. TRIM25 expression was down-regulated[8]. TRIM25 is thought to target 14-3-3 σ , a cell cycle regulator, for proteolysis and promoted breast cancer growth[5,9]. Little is known about the expression and functions of TRIM25 in GC. We showed that the expression level of TRIM25 mRNA was higher in GC tissues than in normal tissues. Taken together, these results suggest that TRIM25 could regulate gastric carcinogenesis and may serve as a potential target for antineoplastic therapies
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