Our previous study showed that TRIM could target

Our previous study showed that TRIM31 could target TSC1-TSC2 complex and contributed to the clinical cancer progression [6]. In this study, we showed that TRIM31 could directly target p53 for ubiquitous degradation and further mediated anoikis-resistance of HCC cells. To further clarify the role of these targets in the development of HCC, we test the interaction between TRIM31 and p53 in anchored HCC cells. Our data showed that TRIM31 could also induce ubiquitous degradation of p53 in normal condition without anchorage deprival (data not shown). Thus our study indicated that p53 was a universal target of TRIM31 in the progression of hepatocarcinoma, and TRIM31 could target both TSC1/TSC2-mTORC1 pathway and p53-AMPK pathway for its oncogenic role in HCC progression.
Acknowledgments We thank Dr. Carlo Riccardi(University of Pavia) for providing the p53 plasmid. This study was supported by the National Natural Science Foundation of China (No. 81472269, No. 81672391, and No. 81602550) and the Major Innovation Project of Shandong Province (No. 2018CXGC1217).
Introduction Aromatic-medicinal plants, which have been used in folk medicine for centuries to treat several disorders all over the world, are natural resources presenting an important economic potential in health and wellness. This added value is directly related to the extract composition. Plants have unbounded ability to synthesize aromatic substances such as polyphenols, mainly flavonoids and phenolic acids, which exhibit antioxidant capacity (Zamorano-Ponce, Fernández, Vargas, Rivera, & Carballo, 2004). Reactive oxygen biotin-LC-LC-tyramide (ROS) have been related with the mediation of several pathological processes, including cancer, obesity, cardiovascular and inflammatory diseases. Phenolic compounds can help to limit the oxidative damage caused by ROS either by acting directly on ROS or by stimulating endogenous defence systems (Tsao, 2010). It is known that many infusions from natural sources have plenty of these bioactive compounds, and consequently it is reasonable to determine whether plants have the capacity to prevent disorders related with oxidative stress (Lasagni Vitar, Reides, Ferreira, & Llesuy, 2014). In this context, the Verbenaceae family is composed of approximately 2000 species of wide geographical distribution and it is highlighted by including species mainly used in popular medicine. Among the most important, Lippia citriodora also called lemon verbena grows spontaneously in South America and is cultivated in northern Africa and southern Europe. The leaves of this species are traditionally utilized to treat many digestive disorders due to their anti-inflamatory, analgesic, antipyretic, tonic and stimulating effects (Oliva et al., 2010) and their content related to a large number of polar compounds such as phenylpropanoids, flavonoids, phenolic acids, and iridoid glycosides, being verbascoside the most abundant (Quirantes-Piné, Funes, Micol, Segura-Carretero, & Fernández-Gutiérrez, 2009). AMPK has been revealed to be involved in the regulation of carbohydrate and lipid metabolism and, meanwhile, AMPK activation stimulates ATP production by increasing fatty acid oxidation, muscle glucose transport, mitochondrial biogenesis and caloric intake (Bijland et al., 2013, Carling et al., 2012). In this sense, it has been reported the effect of polyphenols from olive-tree leaves extract by decreasing intracellular lipid accumulation through AMPK-dependent mechanisms in a hypertrophic and insulin resistant adipocyte model (Jiménez-Sánchez et al., 2017). Previously, our studies revealed that polyphenols from L. citriodora extract decreased NF-κB and increased adiponectin protein levels. Further, the anti-inflammatory action of adiponectin was accompanied by the down-regulation of selected inflammatory genes and a significant activation of AMPK in hypertrophic adipocytes. This is important because the ability of polyphenols to act on both, adiponectin and AMPK, may represent important regulators of glucose and lipid metabolism, modulators of inflammation, oxidative stress and insulin resistance and consequently a therapeutic opportunity in the management of obesity (Herranz-López et al., 2015).