Abstract
BackgroundTripartite Motif-Containing 24 (TRIM24) is a member of the tripartite motif family. TRIM24 is claimed aberrantly activated in a number of cancers, such as breast cancer, prostate cancer and lung cancer. However, the expression of TRIM24 in epithelial ovarian cancer (EOC) and its relationship with prognosis remain unclear. In this study, we investigated the expression pattern and underlying clinical significance of TRIM24 in EOC.ResultsData from Oncomine and immunohistochemistry of tissue samples demonstrated that TRIM24 expression was obviously elevated in ovarian carcinoma compared with normal ovary tissues. Elevated TRIM24 expression was closely correlated with serum CA-125 (P = 0.0294), metastasis (P = 0.0022), FIGO (International Federation of Gynecology and Obstetrics) stage (P = 0.0068) and Ki-67 level (P = 0.0395). Kaplan–Meier survival analysis found that TRIM24 expression increased inversely with the clinical prognosis of patients with EOC. Moreover, colony formation and CCK-8 assays showed that TRIM24 promoted EOC cell growth, and tumorigenic experiments in nude mice showed that TRIM24 knockdown inhibited tumor growth in vivo. The Spearman’s correlations revealed that the expression of TRIM24 was significantly correlated with levels of Ki-67 (P = 0.01), at a correlation coefficient of 0.517. Wound-healing and transwell migration assays demonstrated TRIM24 facilitated cell migration. Mechanism studies showed that TRIM24 could promote the phosphorylation level of Akt and the process of EMT.ConclusionOur results confirmed that TRIM24 could predict poor prognosis of EOC patients and promote tumor progression by regulating Akt pathway and EMT. TRIM24 may be used as a new prognostic marker for EOC and may provide a new strategy for targeted therapy of epithelial ovarian cancer.
Highlights
Tripartite Motif-Containing 24 (TRIM24) is a member of the tripartite motif family
Expression of TRIM24 in epithelial ovarian cancer tissues Firstly, we analyzed TCGA Ovarian and TCGA Ovarian 2 database derived from Oncomine to investigate the expression pattern of TRIM24 in Epithelial ovarian cancer (EOC)
These results suggested that TRIM24 might play an oncogene role in the tumorigenesis and development of EOC
Summary
Tripartite Motif-Containing 24 (TRIM24) is a member of the tripartite motif family. TRIM24 is claimed aberrantly activated in a number of cancers, such as breast cancer, prostate cancer and lung cancer. The expression of TRIM24 in epithelial ovarian cancer (EOC) and its relationship with prognosis remain unclear. We investigated the expression pattern and underlying clinical significance of TRIM24 in EOC. Tripartite Motif-Containing 24 (TRIM24) has characteristic of the TRIM family of proteins, amino-terminal RBCC domains (Ring, B-Box, Coiled-Coil), and a TIF1 sub-family-defining PHD-bromodomain, it is an E3 ubiquitin ligase as well as a transcription co-regulator [4, 5]. Its N-terminal TRIM motif includes an important zinc-binding domain-the RING region, which is involved in ubiquitylation and degradation of the major transcription factor p53 [6, 7]. Through its conserved LxxLL motif TRIM24 can mediate transcriptional control by interacting with the activation function 2 (AF-2) regions of several nuclear receptors, such as the estrogen, retinoic acid, vitamin D3 receptors and progesterone receptors [9,10,11]
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