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RNF214 is an understudied ubiquitin ligase with little knowledge of its biological functions or protein substrates. Here we show that the TEAD transcription factors in the Hippo pathway are substrates of RNF214. RNF214 induces non-proteolytic ubiquitylation at a conserved lysine residue of TEADs, enhances interactions between TEADs and YAP, and promotes transactivation of the downstream genes of the Hippo signaling. Moreover, YAP and TAZ could bind polyubiquitin chains, implying the underlying mechanisms by which RNF214 regulates the Hippo pathway. Furthermore, RNF214 is overexpressed in hepatocellular carcinoma (HCC) and inversely correlates with differentiation status and patient survival. Consistently, RNF214 promotes tumor cell proliferation, migration, and invasion, and HCC tumorigenesis in mice. Collectively, our data reveal RNF214 as a critical component in the Hippo pathway by forming a signaling axis of RNF214-TEAD-YAP and suggest that RNF214 is an oncogene of HCC and could be a potential drug target of HCC therapy. RNF214 ubiquitin ligase is understudied. Here the authors show RNF214 promotes hepatocellular carcinoma progression by inducing non-proteolytic ubiquitylation of TEADs and activating YAP signaling pathway. [ABSTRACT FROM AUTHOR]

An adaptive dynamic surface control (DSC) scheme using event triggering mechanism and barrier Lyapunov function (BLF) to constraint state variables and solve energy saving issues is proposed for multi-agent systems (MASs). Furthermore, invented a control algorithm that uses the event-triggered mechanism for not only decrease the number of information exchanges between agents significantly but also decreased utilization of electricity and communication expenses in the control process. DSC and full-state constraints are used to solve the "complexity explosion" problem of the traditional back-stepping method. Simulation and semi-physical experimental platforms were constructed to verify the proposed algorithm is valid. [ABSTRACT FROM AUTHOR]

In this study, the second-order model, Fick's second law of diffusion, and the Peleg model were used to evaluate the extraction kinetic model of polysaccharide (CPP) from Codonopsis pilosula. The characteristic functional groups, surface structure, and physical and chemical properties of CPP were analyzed by multi-spectroscopic and microscopic techniques. The results showed that the extraction process agreed well with the second-order model, Fick's second diffusion law, and Peleg model. Rheological tests showed that CPP exhibited different viscosity changes under different conditions (Solution viscosity was inversely proportional to temperature, time, etc.; proportional to polysaccharide concentration, Na+ content, etc.). CPP was composed of molecular aggregates composed of small particles, with more pore structure and basically completely decomposed at 130 °C. The hypoglycemic study showed that CPP had a strong inhibitory effect on α-glycosidase than α-amylase. The morphology and subsequent structural features, anti-diabetic potential, and rheological properties of CPP were revealed to provide a theoretical basis for the development of pharmaceutical preparations or health food and functional food for the treatment of diabetes. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to investigate the relationship between matrix metalloproteinase-7 (MMP-7) expression and the clinical and pathological characteristics of salivary adenoid cystic carcinomas (SACC) of the palatal minor salivary gland. Methods: In this study, 58 samples of SACC and 10 samples of normal salivary gland tissue were examined. Immunohistochemistry was used to detect MMP-7 and vascular endothelial growth factor A (VEGF-A) expression in SACC and normal tissues. The clinical and pathological characteristics of the patients with SACC were collected. Results: Of the 58 SACC samples, 44 were positive for MMP-7, and the expression rate was 75.9%. No expression was detected in the 10 normal salivary gland tissues. The level of MMP-7 expression in the SACC and normal samples was significantly different. The level of expression of MMP-7 in the SACC samples did not correlate with age, sex or pathological type but did correlate with pathological grade, nerve infiltration and clinical stage. There was a positive correlation between VEGF-A and MMP-7 expression. Conclusions: The SACC samples showed high expression of MMP-7, which was associated with tumour differentiation, invasiveness and clinical stage. The detection of MMP-7 positively correlated with the detection of VEGF-A in SACC. [ABSTRACT FROM AUTHOR]

Objective: To explore the VEGF-A expression in salivary gland adenoid cystic carcinoma tissues and detect the relationship between the mechanism of occurrence, development and metastasis of jaws with salivary gland adenoid cystic carcinoma and VEGF-A expression. Methods: Paraffin samples from 58 cases of SACC of the palate and ten cases of normal salivary gland tissues were collected. The expression levels of VEGF-A protein were detected using the immunohistochemistry EnVision system. Results: Among the 58 cases, there were 20 cases of the cribriform type, 17 cases of the tubular type, and 21 cases of the solid type. There were 9 cases with lymph node metastasis and 21 cases without lymph node metastasis. And there were 8 cases of T1, 15 cases of T2, and 7 cases of T3/T4. The positive expression rate of VEGF-A in SACC of the palate was 74.1%, which was higher than that found in normal salivary gland tissues (10%). The VEGF-A was localized in the cytoplasm/cell membrane. Conclusion: VEGF-A is highly expressed in SACC of the palate. The level of expression is closely related to the pathological grade, lymph node metastasis, and clinical stage of the tumor, and it can thus be used as an important indicator for judging the biological behavior of SACC of the palate. [ABSTRACT FROM AUTHOR]

How cancer cells cope with high levels of replication stress during rapid proliferation is currently unclear. Here, we show that macrophage migration inhibitory factor (MIF) is a 3' flap nuclease that translocates to the nucleus in S phase. Poly(ADP-ribose) polymerase 1 co-localizes with MIF to the DNA replication fork, where MIF nuclease activity is required to resolve replication stress and facilitates tumor growth. MIF loss in cancer cells leads to mutation frequency increases, cell cycle delays and DNA synthesis and cell growth inhibition, which can be rescued by restoring MIF, but not nuclease-deficient MIF mutant. MIF is significantly upregulated in breast tumors and correlates with poor overall survival in patients. We propose that MIF is a unique 3' nuclease, excises flaps at the immediate 3' end during DNA synthesis and favors cancer cells evading replication stress-induced threat for their growth. Replication stress is associated with cancer formation and progression. Here the authors reveal that the macrophage migration inhibitory factor (MIF) functions as 3' flap nuclease involved in resolving replication stress affecting overall tumor progression. [ABSTRACT FROM AUTHOR]

Lymph node metastasis is an important factor determining the outcome of colorectal cancer. Although epithelial-to-mesenchymal transition (EMT), TNF-α and microRNA (miRNA) have been found to play important roles in lymph node metastasis, the underlying molecular mechanism remains unclear. Here we reported that high expression of microRNA-19a (miR-19a) was associated with lymph node metastasis and played an important role in TNF-α-induced EMT in colorectal cancer (CRC) cells. We analyzed miR-19a expression in surgical tissue specimens from 11 CRC patients and 275 formalin-fixed, paraffin-embedded CRC patients. We found that miR-19a was up-regulated in CRC tissues and high expression of miR-19a was significantly associated with lymph node metastasis. We further analyzed miR-19a lymph node metastasis signature in an external validation cohort of 311 CRC cases of the TCGA. MiR-19a was found to be significantly associated with lymph node metastasis in rectal cancer. In vitro, we showed that overexpression of miR-19a in human CRC cell lines promoted cell invasion and EMT. Furthermore, miR-19a was up-regulated by TNF-α and miR-19a was required for TNF-α-induced EMT and metastasis in CRC cells. Collectively, miR-19a played an important role in mediating EMT and metastatic behavior in CRC. It may serve as a potential marker of lymph node metastasis. [ABSTRACT FROM AUTHOR]