No abstract

The beneficial function of gastrodin towards many inflammatory diseases has been identified. This study designed to see the influence of gastrodin in a cell model of chronic obstructive pulmonary disease (COPD). MRC‐5 cells were treated by LPS, before which gastrodin was administrated. The effects of gastrodin were evaluated by conducting CCK‐8, FITC‐PI double staining, Western blot, qRT‐PCR and ELISA. Besides this, the downstream effector and signalling were studied to decode how gastrodin exerted its function. And dual‐luciferase assay was used to detect the targeting link between miR‐103 and lipoprotein receptor‐related protein 1 (LRP1). LPS induced apoptosis and the release of MCP‐1, IL‐6 and TNF‐α in MRC‐5 cells. Pre‐treating MRC‐5 cells with gastrodin attenuated LPS‐induced cell damage. Meanwhile, p38/JNK and NF‐κB pathways induced by LPS were repressed by gastrodin. miR‐103 expression was elevated by gastrodin. Further, the protective functions of gastrodin were attenuated by miR‐103 silencing. And LRP1 was a target of miR‐103 and negatively regulated by miR‐103. The in vitro data illustrated the protective function of gastrodin in LPS‐injured MRC‐5 cells. Gastrodin exerted its function possibly by up‐regulating miR‐103 and modulating p38/JNK and NF‐κB pathways.

No abstract

T-cell factor 4 (TCF-4) is determined to play a crucial role in Wnt/β-catenin signaling pathway activation. The mutations and alternative splice isoforms of TCF-4 can cause cancers and other diseases. The high-mobility group (HMG) box domain of TCF-4 contributes to interacting with DNA motif for transcriptional regulation. However, the impact of the mutations within HMG box of TCF-4 on the genomic binding pattern is poorly investigated. Herein, we generated non–small cell lung cancer (NSCLC) cell line A549 with stably overexpressed TCF-4 with HMG box hot spot mutation (10th exon partial deletion), and conducted TCF-4 and β-catenin chromatin immunoprecipitation sequence to explore the differential genomic binding patterns. Our results revealed that TCF-4 lost 19365 but gained 1724 peaks, and β-catenin lost 4035 but gained 5287 peaks upon mutant TCF-4 compared with the wild type (log2FC > 1 or < -1, FDR<0.01). The transcriptional levels of the genes associated with these differential peaks such as H3F3C, KRT1, KRT14, MMp1, and MMP15 were all found to strongly change responding to TCF-4 binding (P < 0.05). Furthermore, A549 cells with TCF-4 mutation displayed a more compromising tumor characterization on cell proliferation and invasion. Our data determined the important role of TCF-4 in gene transcription controlling and provided the gain function evidence of TCF-4 caused by the TCF-4 mutation in NSCLC.