"Ap-1 binding site"

BACKGROUND/AIM: A role for cold-shock domain (CSD) proteins in abnormal cell proliferation has been suggested in the literature. The aim of this study was to investigate the effect of hepatocyte growth factor (HGF)-induced up-regulation of CSD protein A (CSDA) expression on vascular endothelial growth factor (VEGF) expression and its role in gastric cancer cell invasion and proliferation. MATERIALS AND METHODS: We assessed effects on two gastric cancer cell lines using reverse transcription-polymerase chain reaction, western blotting, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, and CSDA knockdown with short hairpin RNA...

In this study we observed that human GD1c/GT1a/GQ1b synthase (hST8Sia V) is particularly expressed in human glioblastoma cells. To address the mechanism regulating human glioblastoma-specific gene expression of the hST8Sia V, after the transcription start site (TSS) was identified by the 5'-rapid amplification of cDNA end with total RNA from human glioblastoma U87MG cells, the 5'-flanking region (2.5 kb) of the hST8Sia V gene was isolated and its promoter activity was examined. By luciferase reporter assay, this 5'-flanking region revealed strong promoter activity in only U-87MG cells, but not in other tissue-derived cancer cells...

The age-dependent loss of neuronal plasticity is a well-known phenomenon that is poorly understood. The loss of this capacity for axonal regeneration is emphasized following traumatic brain injury, which is a major cause of disability and death among adults in the US. We have previously shown the intrinsic capacity of magnocellular neurons within the supraoptic nucleus to undergo axonal regeneration following unilateral axotomization in an age-dependent manner. The aim of this research was to determine the age-dependent molecular mechanisms that may underlie this phenomenon...

Glutathione peroxidase 4 (GPX4)-dependent ferroptosis in pancreatic acinar cells plays a critical role in acute pancreatitis (AP). However, potential upstream regulators of GPX4 are not well defined. Here, we observed a marked reduction in acinar GPX4 expression and ferroptotic cell death in mice with cerulein-induced AP. To determine the critical factors involved in acinar cell ferroptosis, pancreas transcriptome data from an AP mouse model were analyzed and overlapped with predicted transcription factors of Gpx4 , and an upregulated transcription factor active protein 1 (AP-1) protein, Jun, was identified...

Platycodin D, a triterpenoid monomer, has been shown to possess an anti-tumor effect on various types of cancer. Although Platycodin D has been reported to suppress tumorigenesis, the detailed underlying mechanism remains elusive. Platycodin D treatment significantly reduced the cell viability, decreased the number of colonies, impaired the mitochondrial function, and induced apoptosis in non-small cell lung cancer (NSCLC) cells. To understand the mechanism by which platycodin D induces apoptosis, the expression levels of apoptosis-related proteins were examined, and we found that the expression of PUMA (p53 upregulated modulator of apoptosis) was upregulated upon platycodin D treatment...

The Ets transcription factor PU.1 is essential for inducing the differentiation of monocytes, macrophages, and B cells in fetal liver and adult bone marrow. PU.1 controls hematopoietic differentiation through physical interactions with other transcription factors, such as C/EBPα and the AP-1 family member c-Jun. We found that PU.1 recruits c-Jun to promoters without the AP-1 binding sites. To address the functional importance of this interaction, we generated PU.1 point mutants that do not bind c-Jun while maintaining normal DNA binding affinity...

Polyamine levels decrease with menopause; however, little is known about the mechanisms regulated by menopause. In this study, we found that among the genes involved in the polyamine pathway, polyamine oxidase ( PAOX ) mRNA levels were the most significantly reduced by treatment with 17β-estradiol in estrogen receptor (ESR)-positive MCF-7 breast cancer cells. Treatment with 17β-estradiol also reduced the PAOX protein levels. Treatment with selective ESR antagonists and knockdown of ESR members revealed that estrogen receptor 2 (ESR2; also known as ERβ) was responsible for the repression of PAOX by 17β-estradiol...

We have developed a mouse DNA methylation array that contains 296,070 probes representing the diversity of mouse DNA methylation biology. We present a mouse methylation atlas as a rich reference resource of 1,239 DNA samples encompassing distinct tissues, strains, ages, sexes, and pathologies. We describe applications for comparative epigenomics, genomic imprinting, epigenetic inhibitors, patient-derived xenograft assessment, backcross tracing, and epigenetic clocks. We dissect DNA methylation processes associated with differentiation, aging, and tumorigenesis...

Natural killer (NK) cells play an important role in recognizing and killing pathogen-infected or malignant cells. Changes in their numbers or activation can contribute to several diseases and pathologies including systemic sclerosis (SSc), an autoimmune disease characterized by inflammation and tissue remodeling. In these patients, increased expression of the AP-1 transcription factor, Fra-2 was reported. In mice ectopic overexpression of Fra-2 (TG) leads to SSc with strong pulmonary fibrosis, pulmonary hypertension, and inflammation...

Intrahepatic cholangiocarcinoma (ICC) is a malignant tumor with poor prognosis while its mechanisms of pathogenesis remain elusive. In this study, we performed systemic epigenomic and transcriptomic profiling via MNase-seq, ChIP-seq and RNA-seq in normal cholangiocyte and ICC cell lines. We showed that active histone modifications (H3K4me3, H3K4me1 and H3K27ac) were less enriched on cancer-related genes in ICC cell lines compared to control. The region of different histone modification patterns is enrichment in sites of AP-1 motif...

The causative gene of Fukuyama congenital muscular dystrophy (fukutin) is involved in formation of the basement membrane through glycosylation of alpha-dystroglycan. However, there are other proposed functions that have not been fully understood. Using cultured astrocytes (1321N1), we found nuclear localization of fukutin and a positive relationship between fukutin expression and cell proliferation. Among potential proteins regulating cell proliferation, we focused on cyclin D1, by reverse-transcription polymerase chain reaction, Western blotting, immunocytochemistry, enzyme-linked immunosorbent assay (ELISA), and sandwich ELISA...

Human Dachshund homolog 1 (DACH1) is usually defined as a tumor suppressor, which plays an influential role in tumor growth and metastasis in a variety of cancer cells. However, the underlying mechanisms in these process are not yet fully clarified. In this study, DACH1 inhibited the invasion and metastasis of breast cancer cells by decreasing MMP9 expression. Mechanistically, DACH1 represses the transcriptional level of MMP9 by interacting with p65 and c-Jun at the NF-κB and AP-1 binding sites in MMP9 promoter respectively, and the association of DACH1 and p65 promote the recruitment of HDAC1 to the NF-κB binding site in MMP9 promoter, resulting in the reduction of the acetylation level and the transcriptional activity of p65...

In crustaceans, innate immunity serves as the frontline of defense against microbes. Alkaline phosphatases (ALPs) and acid phosphatases (ACPs) are essential enzymes that play a significant role in crustaceans' immune defenses. However, the function and transcriptional regulation of the alp and acp genes in the Scylla paramamosain, an important aquaculture species in China, have not been elucidated. In this study, the full-length cDNAs of Spalp and Spacp were identified, which consist of 2,718 bp and 3,768 bp, encoding 579 and 452 amino acids, respectively...

Liver fibrosis is caused by repetitive hepatic injury. Regulated in development and DNA damage response 1 (REDD1) gene is induced by various stresses and has been studied in cell proliferation and survival. However, the role of REDD1 in hepatic stellate cell activation and hepatic fibrogenesis has not yet been investigated. In the current study, we examined the effect of REDD1 on hepatic fibrogenesis and the underlying molecular mechanism. REDD1 protein was upregulated in the activated primary hepatic stellate cells and transforming growth factor-β (TGF-β)-treated LX-2 cells...

Regulatory T cell (Treg) therapy is a promising curative approach for a variety of immune-mediated conditions. CRISPR-based genome editing allows precise insertion of transgenes through homology-directed repair, but its use in human Tregs has been limited. We report an optimized protocol for CRISPR-mediated gene knockin in human Tregs with high-yield expansion. To establish a benchmark of human Treg dysfunction, we target the master transcription factor FOXP3 in naive and memory Tregs. Although FOXP3-ablated Tregs upregulate cytokine expression, effects on suppressive capacity in vitro manifest slowly and primarily in memory Tregs...

Steroid hormones influence diverse biological processes throughout the animal life cycle, including metabolism, stress resistance, reproduction, and lifespan. In insects, the steroid hormone, 20-hydroxyecdysone (20E), is the central hormone regulator of molting and metamorphosis, and plays roles in tissue morphogenesis. For example, amnioserosa contraction, which is a major driving force in Drosophila dorsal closure (DC), is defective in embryos mutant for 20E biosynthesis. Here, we show that 20E signaling modulates the transcription of several DC participants in the amnioserosa and other dorsal tissues during late embryonic development, including zipper, which encodes for non-muscle myosin...

BACKGROUND: Several studies have reported that hypoxia plays a pathological role in severe asthma and tissue fibrosis. Our previous study showed that hypoxia induces A disintegrin and metalloproteinase 17 (ADAM17) expression in human lung fibroblasts. Moreover, preadipocyte factor 1 (Pref-1) is cleaved by ADAM17, which participates in adipocyte differentiation. Furthermore, Pref-1 overexpression is involved in tissue fibrosis including liver and heart. Extracellular signal-regulated kinase (ERK) could active downstram gene expression through polyoma enhancer activator 3 (PEA3) phosphorylation...

Uncontrolled recurrence and metastasis are important reasons for the high mortality rate of malignant tumors. Vimentin is positively correlated with the degree of malignancy of cancer cells. Vimentin is also highly expressed in colorectal cancer (CRC) cells and plays a critical role in the metastasis and prognosis of CRC. However, the molecular mechanism of vimentin in the progression of CRC is incompletely understood. Therefore, the most active regions (nucleotides: 785-1085 nt) of the vimentin promoter in CRC were identified using luciferase experiments...

Nogo-B is an important regulator of tumor angiogenesis. Expression of Nogo-B is remarkably upregulated in multiple tumor types, especially hepatocellular carcinoma (HCC). Here, we show the transcriptional regulation mechanisms of Nogo-B in liver cancer. In response to hypoxia, expression of Nogo-B significantly increased in HCC tissues and cells. The distal hypoxia-responsive element (HRE) in the promoter was essential for transcriptional activation of Nogo-B under hypoxic conditions, which is the specific site for HIF-1α binding...

In solid cancers, high expression of the cellular prion protein (PrPC) is associated with stemness, invasiveness, and resistance to chemotherapy, but the role of PrPC in tumor response to radiotherapy is unknown. Here, we show that, in neuroblastoma, breast, and colorectal cancer cell lines, PrPC expression is increased after ionizing radiation (IR) and that PrPC deficiency increases radiation sensitivity and decreases radiation-induced radioresistance in tumor cells. In neuroblastoma cells, IR activates ATM that triggers TAK1-dependent phosphorylation of JNK and subsequent activation of the AP-1 transcription factor that ultimately increases PRNP promoter transcriptional activity through an AP-1 binding site in the PRNP promoter...