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cAMP responsive element binding protein 3 (CREB3), belonging to bZIP family, was reported to play multiple roles in various cancers, but its role in hepatocellular carcinoma (HCC) is still unclear. cAMP responsive element binding protein 3 like 3 (CREB3L3), another member of bZIP family, was thought to be transcription factor (TF) to regulate hepatic metabolism. Nevertheless, except for being TFs, other function of bZIP family were poorly understood. In this study, we found CREB3 inhibited growth and metastasis of HCC in vitro and in vivo. RNA sequencing indicated CREB3 regulated AKT signaling to influence HCC progression. Mass spectrometry analysis revealed CREB3 interacted with insulin receptor (INSR). Mechanistically, CREB3 suppressed AKT phosphorylation by inhibiting the interaction of INSR with insulin receptor substrate 1 (IRS1). In our study, CREB3 was firstly proved to affect activation of substrates by interacting with tyrosine kinase receptor. Besides, CREB3 could act as a TF to transactivate RNA‐binding motif protein 38 (RBM38) expression, leading to suppressed AKT phosphorylation. Rescue experiments further confirmed the independence between the two functional manners. In conclusion, CREB3 acted as a tumor suppressor in HCC, which inhibited AKT phosphorylation through independently interfering interaction of INSR with IRS1, and transcriptionally activating RBM38. [ABSTRACT FROM AUTHOR]

Background: Long non‐coding RNAs (LncRNAs) have been demonstrated to associate with a variety of cancers. However, the mechanisms of LncRNAs in hepatocellular carcinoma (HCC) progression are still not fully clarified. Methods: LINC01608 expression level in HCC and adjacent normal tissues was detected by real‐time‐quantitively PCR (RT‐qPCR) in clinical samples and in situ hybridization (ISH) in tissue microarray. Several functional assays were performed to determine the biological effects of LINC01608 in HCC cells in vitro, while subcutaneous xenograft models and lung metastasis models in nude mice and immunohistochemistry (IHC) results showed the role of LINC01608 in HCC progression in vivo. The combination of LINC01608 with miR‐875‐5p and target genes was elucidated by dual‐luciferase report assays, RNA immunoprecipitation (RIP) assays and fluorescence in situ hybridization (FISH) assays. Finally, bioinformatics analysis and chromatin immunoprecipitation (CHIP) were performed to investigate the mechanism of Yin Yang‐1 (YY1) regulating LINC01608 transcription. Results: LINC01608 was overexpressed in HCC tissues, and high LINC01608 expression predicted poor overall survival (OS) and disease‐free survival (DFS) in HCC patients. LINC01608 could promote HCC cell proliferation, migration, invasion and epithelial‐mesenchymal transition (EMT) in vitro and in vivo. Furthermore, we demonstrated that LINC01608 could sponge to miR‐875‐5p and activate the EGFR/ERK pathway. Moreover, we identified transcriptional factor YY1 could bind to the promoter of LINC01608 and induce its transcription. Conclusion: LINC01608 could serve as a promising prognostic biomarker of HCC. YY1‐activated LINC01608 could promote HCC progression by associating with miR‐875‐5p to induce the EGFR/ERK signalling pathway. This discovery might provide therapeutic strategies for HCC. [ABSTRACT FROM AUTHOR]

Objective: We studied the effects of a plant fermentation extract on destroying biofilms of P. aeruginosa, to provide basic information for treatment of P. aeruginosa related infection diseases., Methods: Strains of P. aeruginosa in clinical specimens were isolated by streaking plate method and identified by PCR and sequencing. Virulence factors were examined using reporter strains, and biofilms were measured by test tube method and a confocal laser scanning microscopy., Results: A total of 16 strains of P. aeruginosa were isolated from clinical specimens from a local hospital, among them PA007 strain showed a maximum response when treated with plant fermentation extract. It shows that 1% plant fermentation extract significantly reduced the production of biofilm, pyocyanine and 3-oxo-C12-HSL (P<0.05). Besides, 1% plant fermentation extract also deceased the bioactivity of LasA protease and survival rate of persisters (P<0.05). The qRT-PCR result indicated that the expressions of lasI and pqsA genes were also markedly inhibited at the presence of 1% plant fermentation extract (P<0.05)., Conclusion: The studied plant fermentation extract has anti-infection effect against some P. aeruginosa strains, suggesting a great potential to work as natural antibiotics.