RNA-binding protein tristetraprolin (TTP) plays a fundamental role in various physiological and pathological processes including differentiation, reprogramming, metabolism, proliferation, pluripotency, tumorigenesis and immunity. Due to its ability to bind and target ARE-containing mRNAs for rapid degradation, TTP down-regulates the expression of a mass of critical genes, thereby functioning as cancer suppressor gene. The loss of TTP has been reported in several human cancers and is relevant to poor prognosis. Recent research shows that TTP also has an emerging significant role in immunity. The aim of this paper is to provide an overview of various roles of TTP in human cancers and immunity. We summarize TTP deficiency in several cancers and discuss that the lack of TTP can influence tumor progression at different aspects such as promoting cancer cell proliferation; accelerating cell cycle; improving survivability and resisting cell death; inducing angiogenesis; activating invasion and metastasis; inducing epithelial-mesenchymal transition; and deregulating cellular energetics. We also pay attention to novel understanding of the relationship between TTP and immunity. Finally, due to its vital role, the disorder of TTP in both cancer and immune cells receives increasing attention and we overview current thinking about regulatory mechanisms of TTP itself expression. This knowledge may contribute to TTP becoming a diagnostic marker for cancer or immune-related diseases and a possible therapeutic target.

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Glycyrrhizic acid (GA) is the main active ingredient extracted from Chinese herb licorice root, and it shows anti-tumor effects in many cancer types, while its role in gastric cancer (GC) is still unknown. In this study, we evaluated the effects of GA on GC cells and explored the underlying mechanisms. Methods: The anti-proliferation effect of GA on GC cells was assessed by CCK-8, colony formation, and EdU assay. The effects of GA on cell cycle and apoptosis were detected by flow cytometer. Western blotting was performed to explore the underlying mechanisms. Results: Our results showed that GA had a time-and dose-dependent inhibitory effect on proliferation of GC cells. Flow cytometer analysis demonstrated that GA would lead to G1/ S-phase arrest and apoptosis. GA treatment down-regulated the levels of G1 phase-related proteins, including cyclin D1, D2, D3, E1, and E2. In terms of apoptosis, GA treatment upregulated the levels of Bax, cleaved PARP, and pro-caspase-3,-8,-9, but did not influence their cleavage patterns. The expression of Bcl-2, survivin and p65 was attenuated after treatment. Besides, GA would down-regulate the phosphorylation of PI3K/AKT pathway. Conclusion: This study focused on inhibitory effect of GA on GC cells by inducing cell cycle arrest and apoptosis. Several important cyclins-and apoptosis-related proteins were involved in the regulation of GA to GC cells, and phosphorylated PI3K and AKT were attenuated. The results of this study indicated that GA is a potential and promising anticancer drug for GC.

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Breast cancer is one of the most frequently diagnosed cancer in women and is the major cause of most cancer-related deaths. We previously reported that Brachyury, as a sensitive and specific marker, has been verified to involve in the process of carcinogenesis and progression of breast cancer, but the mechanism by which Brachyury promotes breast cancer cells proliferation and migration still remains less clear. In this study, we identified that Brachyury was markedly increased in breast cancer compared with the adjacent tissues. We have also shown that Brachyury knockdown could decrease the proliferation and migration capability in breast cancer cells both in vitro and in vivo. Finally, we found an important transcriptional factor, E2F3, which is a direct downstream target gene of Brachyury by chromatin immunoprecipitation (ChIP) analysis. Knockdown of E2F3 also decreased breast cancer cell proliferation and migration. Taken together, we reported that Brachyury may act as an oncogenic role in the progression of breast cancer by positively-regulating E2F3 expression.

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