DNA and cell biology最新文献

Previous studies have shown that interferon gene-stimulating protein (STING) is essential for IFN-γ-inducible protein 16 (IFI16) as the DNA sensor and RNA sensor to induce transcription of type I interferon (IFN-I) and is essential for IFI16 to synergize with DNA sensor GMP-AMP (cGAMP) synthase (cGAS) in induction of IFN-I transcription. While other and our previous studies have shown that IFI16 enhanced retinoic acid-inducible gene I (RIG-I)-, which was an RNA sensor, and mitochondrial antiviral signaling (MAVS)-, which was the adaptor protein of RIG-I, induced production of IFN-I, so we wonder whether IFI16 regulates the signal pathway of RNA-RIG-I-MAVS-IFN-I in a STING-dependent manner. We used HEK 293T cells, which did not express endogenous STING and were unable to mount an innate immune response upon DNA transfection and found that IFI16 could enhance RIG-I- and MAVS-mediated induction of IFN-I in a STING-independent way. Furthermore, we found that upregulation of the expression of NF-kappa-B essential modulator (NEMO) by IFI16 was not the mechanism that IFI16 regulated the induction of IFN-I. In conclusion, we found that IFI16 regulated the signal pathway of RNA-RIG-I-MAVS-IFN-I in a STING-independent manner.

Cisplatin (DDP) resistance frequently occurs in gastric cancer (GC) therapy. Tanshinone I is a liposoluble phenanthraquinone compound present in the roots of Salvia miltiorrhiza Bunge (Danshen). In this study, we aimed to explore the effects of tanshinone I on modulating DDP resistance of GC cells in vitro and in vivo. DDP-resistant GC cell models (BGC823/DDP and SGC7901/DDP) were established, and their viability, proliferation, migration, lactate dehydrogenase activity, reactive oxygen species (ROS) generation, and pyroptosis were assessed after DDP treatment with or without tanshinone I. In addition, a mouse model with subcutaneously transplanted GC tumors was established to confirm the effects of tanshinone I and DDP on tumor growth and cell pyroptosis. The results revealed that tanshinone I inhibited DDP-resistant GC cell proliferation and migration; increased intracellular ROS levels; and activated cell pyroptosis by enhancing the levels of cleaved caspase-8, cleaved caspase-3, GSDME-NT, phospho-IKK-α/β, and nuclear factor kappa-B (NF-κB). GSDME knockdown weakened these effects of tanshinone I on DDP-resistant GC cells. Furthermore, DDP combined with tanshinone I inhibited the growth of subcutaneously transplanted GC tumors in mice by reducing cell proliferation and inducing pyroptosis. In conclusion, tanshinone I reversed DDP resistance of GC cells by stimulating pyroptosis, by activating NF-κB/caspase-3(8)/GSDME signaling pathway.

The complement system is a family of proteins that facilitate immune resistance by attacking microbes to decrease pathogen burden. As a result, deficiencies of certain complement proteins result in recurrent bacterial infections, and can also result in acute lung injury (ALI). We and others have shown that C3 is present in both immune and nonimmune cells, and modulates cellular functions such as metabolism, differentiation, cytokine production, and survival. Although the emerging roles of the complement system have implications for host responses to ALI, key questions remain vis-a-vis the lung epithelium. In this review, we summarize our recent article in which we reported that during Pseudomonas aeruginosa-induced ALI, lung epithelial cell-derived C3 operates independent of liver-derived C3. Specifically, we report the use of a combination of human cell culture systems and global as well as conditional knockout mouse models to demonstrate the centrality of lung epithelial cell-derived C3. We also summarize recent articles that have interrogated the role of intracellular and/or locally derived C3 in host defense. We propose that C3 is a highly attractive candidate for enhancing tissue resilience in lung injury as it facilitates the survival and function of the lung epithelium, a key cell type that promotes barrier function.

To investigate the functional differences of angiopoietin-related protein 4 (ANGPTL4) transcripts in hepatocellular carcinoma (HCC) cells. By transfecting ANGPTL4-Transcript 1 and ANGPTL4-Transcript 3 overexpression vectors into HepG2 and Huh7 cell lines with ANGPTL4 knockdown, the effects of overexpression of two transcripts on cell viability, invasion, migration, and apoptosis were analyzed. The expression of two transcripts was compared in human liver cancer tissue, and their effects on tumor development were validated in vivo experiments in mice. Compared with control, the overexpression of ANGPTL4-Transcript 1 had no significant effect on viability, invasion, healing, and apoptosis of HepG2 and Huh7 cells. However, these two cell lines overexpressing ANGPTL4-Transcript 3 showed remarkably enhanced cell viability, invasive and healing ability, and decreased apoptosis ability. Furthermore, the mRNA level of ANGPTL4-Transcript 3 was significantly increased in human HCC tissues and promoted tumor growth compared with Transcript 1. Different transcripts of gene ANGPTL4 have distinct effects on HCC. The abnormally elevated Transcript 3 with the specific ability of promoting HCC proliferation, infiltration, and migration is expected to become a new biological marker and more precise intervention target for HCC.