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      TRIM15 Exerts Anti-Tumor Effects Through Suppressing Cancer Cell Invasion in Gastric Adenocarcinoma

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          Abstract

          Backgrounds

          Recent studies have shown that some members of the tripartite motif-containing protein (TRIM) family function as important regulators in several tumors. However, the clinical significance of TRIM15 in gastric adenocarcinoma has not been elucidated. In the present study, we aimed to examine the expression pattern of TRIM15 and explore whether the TRIM15 expression is correlated with clinicopathological characteristics of patients with gastric adenocarcinoma.

          Material/Methods

          The expression pattern of TRIM15 was examined in gastric adenocarcinoma tissues and adjacent normal stomach tissues by using immunohistochemistry staining. The prognostic role of TRIM15 in gastric cancer patients was evaluated by univariate and multivariate analyses. Clinical outcomes were assessed by the Kaplan-Meier analysis and log-rank test. The effects of TRIM15 on cancer cell proliferation and invasion were tested through cellular experiments.

          Results

          TRIM15 was highly expressed in normal stomach tissues compared to tumor tissues. TCGA database showed that higher TRIM15 RNA transcription indicates poorer overall survival of gastric cancer patients. Besides, low expression of TRIM15 was significantly associated with advanced tumor invasion depth and advanced TNM stage. Moreover, gastric cancer patients with lower KDM5B expression had poorer overall survival, and TRIM15 was identified as an independent prognosis factor according to multivariate analysis. Using the gastric cancer cell lines, we found that overexpression of TRIM15 can inhibits tumor cell invasion.

          Conclusions

          Our study demonstrated that low expression of TRIM15 in gastric adenocarcinoma tissues was significantly associated with poorer prognosis of patients, indicating the potential of TRIM15 as a novel clinical biomarker and therapeutic target.

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          Most cited references29

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          Ubiquitylation at the crossroads of development and disease

          Ubiquitylation is a post-translational modification that modulates protein stability and regulates various cellular signalling pathways and cellular processes, including cell differentiation, proliferation and migration. Recent insights highlight its crucial role in development and how its deregulation is associated with several diseases.
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            Is Open Access

            The Salmonella Effector Protein SopA Modulates Innate Immune Responses by Targeting TRIM E3 Ligase Family Members

            Salmonella Typhimurium stimulates inflammatory responses in the intestinal epithelium, which are essential for its ability to replicate within the intestinal tract. Stimulation of these responses is strictly dependent on the activity of a type III secretion system encoded within its pathogenicity island 1, which through the delivery of effector proteins, triggers signaling pathways leading to inflammation. One of these effectors is SopA, a HECT-type E3 ligase, which is required for the efficient stimulation of inflammation in an animal model of Salmonella Typhimurium infection. We show here that SopA contributes to the stimulation of innate immune responses by targeting two host E3 ubiquitin ligases, TRIM56 and TRIM65. We also found that TRIM65 interacts with the innate immune receptor MDA5 enhancing its ability to stimulate interferon-β signaling. Therefore, by targeting TRIM56 and TRIM65, SopA can stimulate signaling through two innate immune receptors, RIG-I and MDA5. These findings describe a Salmonella mechanism to modulate inflammatory responses by directly targeting innate immune signaling mechanisms.
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              Curcumin Inhibits Gastric Carcinoma Cell Growth and Induces Apoptosis by Suppressing the Wnt/β-Catenin Signaling Pathway

              Background Curcumin has well-known, explicit biological anti-tumor properties. The Wnt/β-catenin signaling pathway plays a central role in tumor cell proliferation and curcumin can regulate the Wnt/β-catenin signaling pathway of several carcinomas. The aim of this study was to investigate the impact of curcumin on the Wnt/β-catenin signaling pathway in human gastric cancer cells. Material/Methods We used 3 gastric cancer cell lines: SNU-1, SNU-5, and AGS. Research methods used were MTT assay, flow cytometry, clonogenic assay, annexin V/PI method, Western blotting analysis, tumor formation assay, and in vivo in the TUNEL assay. Results Curcumin markedly impaired tumor cell viability and induced apoptosis in vitro. Curcumin significantly suppressed the levels of Wnt3a, LRP6, phospho-LRP6, β-catenin, phospho-β-catenin, C-myc, and survivin. Xenograft growth in vivo was inhibited and the target genes of Wnt/β-catenin signaling were also reduced by curcumin treatment. Conclusions Curcumin exerts anti-proliferative and pro-apoptotic effect in gastric cancer cells and in a xenograft model. Inhibition of the Wnt/β-catenin signaling pathway and the subsequently reduced expression of Wnt target genes show potential as a newly-identified molecular mechanism of curcumin treatment.
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                Author and article information

                Journal
                Med Sci Monit
                Med. Sci. Monit
                Medical Science Monitor
                Medical Science Monitor : International Medical Journal of Experimental and Clinical Research
                International Scientific Literature, Inc.
                1234-1010
                1643-3750
                2018
                09 November 2018
                : 24
                : 8033-8041
                Affiliations
                [1 ]Department of Cancer Radiotherapy, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian, P.R. China
                [2 ]Department of Gastrointestinal Surgery, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, P.R. China
                [3 ]2 nd Department of General Surgery, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian, P.R. China
                Author notes
                Corresponding Author: Jianming Hong, e-mail: jie925477766@ 123456163.com
                [A]

                Study Design

                [B]

                Data Collection

                [C]

                Statistical Analysis

                [D]

                Data Interpretation

                [E]

                Manuscript Preparation

                [F]

                Literature Search

                [G]

                Funds Collection

                [*]

                These 2 authors contributed equally to this paper. Weilin Chen and Chuanhui Lu were co-first authors

                Article
                911142
                10.12659/MSM.911142
                6238583
                30412518
                b388289b-075e-4d46-93e5-f9e2f78079cd
                © Med Sci Monit, 2018

                This work is licensed under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International ( CC BY-NC-ND 4.0)

                History
                : 14 April 2018
                : 04 June 2018
                Categories
                Clinical Research

                neoplasm invasiveness,prognosis,stomach neoplasms
                neoplasm invasiveness, prognosis, stomach neoplasms

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