Our results indicated PTEN gene might induce cell invasion and migration via regulating AKT/GSK-3β/β-catenin signaling pathway, playing a vital role in the progression of gastric cancer.
Introduction Gastric cancer (GC) is the sixth most common malignant tumor and the third leading cause of cancer-related death in the world. Studies have shown that TRIM protein can regulate transcription factor activity and is associated with many cancers. However, the role of TRIM11 in gastric cancer remains unclear. Methods TRIM11 protein levels were examined in 36 cases of GC tissues and 4 gastric cancer cell lines. TRIM11 overexpression and knockdown cells were constructed in MGC-803, HGC-27 and SGC-7901, respectively. The biological roles and mechanisms of TRIM11 were examined using CCK8, colony formation, transwell migration assay, invasion assay, Western blotting, Immunohistochemistry and in vivo nude mice experiments. Results We found that TRIM11 was upregulated in gastric cancer tissues and gastric cancer cell lines. Functionally, TRIM11 overexpression increased growth rate, colony formation, invasion and migration ability, EMT and β-catenin protein level and its downstream proteins such as CyclinD1 and C-myc, while TRIM11 knockdown shows the opposite effects. Conclusion In summary, our data show that TRIM11 is overexpressed in GC. TRIM11 promotes proliferation, migration, invasion and EMT of gastric cancer by activating β-catenin signaling.
Combination chemotherapy regimen with several anti-tumor drugs is a strategy to improve outcome. Thymoquinone (TQ) has been reported to exert biological activity on various types of human cancers without obvious toxicity. However, only few studies showed the anti-tumor effects of TQ combination with cisplatin on gastric cancer (GC). Here, we showed pretreatment with 5μM TQ significantly increased the apoptotic effects induced by cisplatin on GC cell lines. Combined treatment of cisplatin with TQ represented a significantly superior tumor suppression effect than either agent alone in a xenograft tumor mouse model. Interestingly, TQ pretreatment following cisplatin caused a significant increase in the levels of PTEN, an obvious decrease in p-AKT, CyclinD1, P-glycoprotein (P-gp), meanwhile, TQ and cisplatin also led to an increase in Bax, Cyt C, AIF, cleaved caspase 9, and cleaved caspase 3, and a decrease in Bcl-2, procaspase-9, procaspase-3. Moreover, results in vitro, showed that a combination of TQ and cisplatin represents a more effective anti-tumor agent than either agent alone in a xenograft tumor mouse model. In conclusion, TQ significantly augments cisplatin-induced anti-tumor effects on gastric cancer both in vitro and in vivo, through inhibiting PI3K/AKT signaling pathway, activating the mitochondrial pathway, and down-regulating P-glycoprotein by up-regulating PTEN gene. TQ might be as a promising candidate as a cancer chemopreventive or chemotherapeutic agent for antineoplastic combination therapy and merits further clinical investigation.
Gastric cancer (GC) is the sixth most common malignancy and the third leading cause of cancer-related death worldwide. 1 Despite the declining morbidity as well as mortality and the significant advances in the comprehension of aetiology and molecular mechanisms, the burden remains high in Asia, Latin America, and eastern and central part of Europe. 2 Although several treatment approaches are applied including surgery, chemotherapy, radiation therapy and molecular targeted therapies, the long-term outcome of GC patients at advanced stages remains disappointing. 3,4 The tumour microenvironment (TME) refers to the environment in which cancer cells originate and develop. Except for cancer cells, the TME consists of different cell types (stromal cells, immune cells, endothelial cells, etc) and extracellular elements (chemokine, cytokines, hormones, etc). 5,6 Emerging evidence suggests that TME cells (including macrophages, T cells and fibroblasts) all play a vital role in the initiation and progression of GC. 7-11 As two major cell types apart from cancer cells in the TME, stromal cells and immune cells exhibit important role in diagnostic and prognostic evaluation of solid tumours. Stromal cells can receive signals sent by cancer cells and then supply the cancer cells with a variety of growth factors, which are essential for invasive growth and metastasis. 12-17 On the other hand, the immune cells in the TME function in a context-dependent way: tumour-antagonizing effects of T cells in ovarian cancer 18-20 and tumour-promoting effects in colorectal cancer. 21,22 Hence, an overall understanding of stromal cells and immune cells
Purpose Gastric cancer (GC) is a common digestive tract malignancy with the sixth and third global incidence and cancer-related deaths, respectively. Microsatellite instability (MSI), account for one of the molecular subtypes of GC, plays an important role in GC and is affected by a sophisticated network of gene interactions. In this study, we aimed to explore the expression pattern and clinical performance of RNF150 in GC patients. Methods Weighted gene co-expression network analysis (WGCNA) was exploited to single out the vital module and core genes in TCGA database. We applied the protein–protein interaction (PPI) and survival analysis to propose and confirm RNF150 as the hub gene. Finally, we utilized IHC to explore the expression pattern of RNF150 in GC patients. Results The turquoise module was adopted as core module for the sake of its highest correlation coefficient and higher module significance value. With the highest weight correlation and standard correlation, RNF150 was finally selected as the hub gene for following validation. In validation, data obtained from the test sets showed a lower expression of RNF150 in MSI GC compared to microsatellite stability (MSS) GC. Moreover, survival analysis shows that MSI GC patients with a lower RNF150 expression level displayed a longer OS time. In 10 GC patients, compared with normal gastric tissues, the protein level of RNF150 was virtually upregulated in GC tissue. Furthermore, RNF150 protein level was decreased in MSI GC samples compared to MSS GC samples, which is in accordance with results we obtained in database. Conclusions RNF150 was determined and confirmed as a novel biomarker in MSI GC. It is expected to be an auspicious prognostic biomarker for MSI GC patients.
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