Mechanistic Insights of hsa-mir-301a Regulation by Tobacco Smoke in Lung Squamous Cell Carcinoma: Evidence From Bioinformatics Analysis.

MicroRNAs play a significant role in the development of cancers, including lung cancer. A recent study revealed that smoking, a key risk factor for lung cancer, increased the levels of hsa-mir-301a in the tumor tissues of patients with lung squamous cell carcinoma (LUSC). The aim of the current study is to investigate the mechanism by which tobacco smoke increases hsa-mir-301a levels in LUSC tumor tissues using bioinformatics analysis.

Smoking-Mediated miR-301a/IRF1 Axis Controlling Immunotherapy Response in Lung Squamous Cell Carcinoma Revealed by Bioinformatic Analysis.

Smoking is an established risk factor for a variety of malignant tumors, the most well-known of which is lung cancer. Various molecular interactions are known to link tobacco smoke exposure to lung cancer, but new data are still emerging on the effects of smoking on lung cancer development, progression, and tumor response to therapy. In this study, we reveal in further detail the previously established association between smoking and hsa-mir-301a activity in lung squamous cell carcinoma, LUSC.

Roles of Interferon Regulatory Factor 1 in Tumor Progression and Regression: Two Sides of a Coin.

IRF1 is a transcription factor well known for its role in IFN signaling. Although IRF1 was initially identified for its involvement in inflammatory processes, there is now evidence that it provides a function in carcinogenesis as well. IRF1 has been shown to affect several important antitumor mechanisms, such as induction of apoptosis, cell cycle arrest, remodeling of tumor immune microenvironment, suppression of telomerase activity, suppression of angiogenesis and others.

Constitutive Androstane Receptor Agonist Initiates Metabolic Activity Required for Hepatocyte Proliferation.

Activation of the constitutive androstane receptor (CAR, NR1I3) by chemical compounds induces liver hyperplasia in rodents. 1,4-Bis[2-(3,5-dichloropyridyloxy)] benzene (TCPOBOP), a mouse CAR agonist, is most often used to study chemically induced liver hyperplasia and hepatocyte proliferation in vivo. TCPOBOP is a potent murine liver chemical mitogen, which induces rapid liver hyperplasia in mice independently of liver injury.

Tumor suppressor PTEN regulation by tobacco smoke in lung squamous-cell carcinoma based on bioinformatics analysis.

Phosphatase and tensin homolog deleted on chromosome 10 (PTEN), is a tumor suppressor inactivated in a variety of human cancers. PTEN alteration correlates with lung squamous-cell carcinoma (LUSC) histology. However, it is still unclear how tobacco smoke regulates PTEN in LUSC tissues.

Role of Tumor Suppressor PTEN and Its Regulation in Malignant Transformation of Endometrium.

Tumor-suppressive effects of PTEN are well-known, but modern evidence suggest that they are not limited to its ability to inhibit pro-oncogenic PI3K/AKT signaling pathway. Features of PTEN structure facilitate its interaction with substrates of different nature and display its activity in various ways both in the cytoplasm and in cell nuclei, which makes it possible to take a broader look at its ability to suppress tumor growth. The possible mechanisms of the loss of PTEN effects are also diverse - PTEN can be regulated at many levels, leading to change in the protein activity or its amount in the cell, while their significance for the development of malignant tumors has yet to be studied.

Promotion of NR1I3-mediated liver growth is accompanied by STAT3 activation.

Background: The constitutive androstane receptor (CAR, NR1I3)-mediated mechanisms regulating hepatocyte proliferation and growth of the liver did not yet experience complete elucidation. We investigated whether STAT3 could be activated in vivo by NR1I3 signaling in mouse liver.

Methods And Results: Using Western blot analysis, immunofluorescence assays and real-time PCR we established the state of STAT3 activation when it comes to the mouse liver subsequent to treatment ofNR1I3 agonist,1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP).

miRNA expression and interaction with the 3'UTR of FMR1 in FRAXopathy pathogenesis.

FRAXopathies are caused by the expansion of the CGG repeat in the 5'UTR of the gene, which encodes the protein responsible for the synthesis of FMRP. This mutation leads to dramatic changes in FMRP expression at both the mRNA and protein levels. Evidence is emerging that changes in mRNA expression can lead to the dysregulation of the miRNAs that target its 3'UTR.

Noncanonical Constitutive Androstane Receptor Signaling in Gene Regulation.

The constitutive androstane receptor (CAR, NR1I3) is extremely important for the regulation of many physiological processes, especially xenobiotic (drug) metabolism and transporters. CAR differs from steroid hormone receptors in that it can be activated using structurally unrelated chemicals, both through direct ligand-binding and ligand-independent (indirect) mechanisms. By binding to specific responsive elements on DNA, CAR increases the expression of its target genes encoding drug-metabolizing enzymes and transporters.

Activation of the Akt pathway by a constitutive androstane receptor agonist results in β-catenin activation.

It is well known that activating the constitutive androstane receptor (CAR, NR1I3) leads to a significant proliferation of liver cells, which suggests that NR1I3 could be a therapeutic target for the partial resection of this organ. Studies describing NR1I3-mediated proliferative pathways could help determine the possible clinical applications of NR1I3 agonists during liver resection or transplantation. Recently, we reported that liver hyperplasia, which results from NR1I3 activation, is mediated by the activation of the Akt signaling pathway.

Promotion of liver growth by CAR is accompanied by Akt pathway activation and FoxM1-Nedd4-mediated repression of PTEN.

Recently, we reported that treatment with the mouse agonist of the constitutive androstane receptor (CAR), 1,4-bis benzene[2-(3,5-dichloropyridyloxy)] (TCPOBOP; a well-known hepatomitogen), reduced PTEN protein levels, leading to Akt activation. Hence, the present study was performed to demonstrate the role of CAR in PTEN regulation and liver growth. Liver hyperplasia caused by CAR activation was confirmed to be mediated by a decrease in PTEN protein level and the activation of the Akt signalling pathway in the liver of mice.

CAR-mediated repression of Cdkn1a(p21) is accompanied by the Akt activation.

It was shown that CAR participates in the regulation of many cell processes. Thus, the activation of CAR causes a proliferating effect in the liver, which provides grounds to consider CAR as a therapeutic target when having a partial resection of this organ. Even though a lot of work has been done on the function of CAR in regulating hepatocyte proliferation, very little has been done on its complex mediating mechanism.

PTEN negative correlates with miR-181a in tumour tissues of non-obese endometrial cancer patients.

The effects of microRNAs on PTEN levels are characteristic for many types of cancer. However, the picture of the correlation between the expression levels of PTEN and its targeting microRNAs in endometrial cancer is not fully presented. Our study investigated and analysed the expression levels of PTEN and PTEN-targeting miR-21, miR-181a, miR-214, miR-301a, and miR-1908 in total of 78 samples, out of which 26 samples were from normal endometrium, whereas the 52 samples were from endometrial cancer samples.

Increased expression of miR-155 and miR-222 is associated with lymph node positive status.

Identification of prognostic molecular markers of breast cancer is extremely important. The spreading out of the primary breast tumour cells to the lymphatic system is at the forefront of symbolising the first signs of distant organ metastasis. Deregulated genes in breast cancer tissues that spread to lymph nodes may show early predictive molecular markers.

Inhibitors of Histone Deacetylases Are Weak Activators of the Gene in Fragile X Syndrome Cell Lines.

Fragile X syndrome is the most common cause of inherited intellectual disability in humans. It is a result of CGG repeat expansion in the 5' untranslated region (5' UTR) of the gene. This gene encodes the FMRP protein that is involved in neuronal development.

Peroxisome proliferator-activated receptor γ activation inhibits liver growth through miR-122-mediated downregulation of cMyc.

Although NR1C3 agonists inhibit cell growth, the molecular mechanism of their action has not been thoroughly characterized to date. A recent study demonstrated that NR1C3 can regulate miR-122 by binding to its promoter. Given that miR-122 can indirectly regulate cMyc-mediated promitogenic signaling by targeting E2f1, we hypothesized that NR1C3 activation inhibits hepatocyte proliferation through miR-122-mediated cMyc downregulation.

Constitutive androstane receptor activation evokes the expression of glycolytic genes.

It is well-known that constitutive androstane receptor (CAR) activation by 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) increases the liver-to-body weight ratio. CAR-mediated liver growth is correlated with increased expression of the pleiotropic transcription factor cMyc, which stimulates cell cycle regulatory genes and drives proliferating cells into S phase. Because glycolysis supports cell proliferation and cMyc is essential for the activation of glycolytic genes, we hypothesized that CAR-mediated up-regulation of cMyc in mouse livers might play a role in inducing the expression of glycolytic genes.

Xenosensor CAR mediates down-regulation of miR-122 and up-regulation of miR-122 targets in the liver.

MiR-122 is a major hepatic microRNA, accounting for more than 70% of the total liver miRNA population. It has been shown that miR-122 is associated with liver diseases, including hepatocellular carcinoma. Mir-122 is an intergenic miRNA with its own promoter.

Expression of p53 target genes in the early phase of long-term potentiation in the rat hippocampal CA1 area.

Gene expression plays an important role in the mechanisms of long-term potentiation (LTP), which is a widely accepted experimental model of synaptic plasticity. We have studied the expression of at least 50 genes that are transcriptionally regulated by p53, as well as other genes that are related to p53-dependent processes, in the early phase of LTP. Within 30 min after Schaffer collaterals (SC) tetanization, increases in the mRNA and protein levels of Bax, which are upregulated by p53, and a decrease in the mRNA and protein levels of Bcl2, which are downregulated by p53, were observed.

CAR-mediated repression of Foxo1 transcriptional activity regulates the cell cycle inhibitor p21 in mouse livers.

1,4-Bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP), an agonist of constitutive androstane receptor (CAR), is a well-known strong primary chemical mitogen for the mouse liver. Despite extensive investigation of the role of CAR in the regulation of cell proliferation, our knowledge of the intricate mediating mechanism is incomplete. In this study, we demonstrated that long-term CAR activation by TCPOBOP increased liver-to-body weight ratio and decreased tumour suppressor Foxo1 expression and transcriptional activity, which were correlated with reduced expression of genes regulated by Foxo1, including the cell-cycle inhibitor Cdkn1a(p21), and upregulation of the cell-cycle regulator Cyclin D1.

Dichlorodiphenyltrichloroethane technical mixture regulates cell cycle and apoptosis genes through the activation of CAR and ERα in mouse livers.

Dichlorodiphenyltrichloroethane (DDT) is a widely used organochlorine pesticide and a xenoestrogen that promotes rodent hepatomegaly and tumours. A recent study has shown significant correlation between DDT serum concentration and liver cancer incidence in humans, but the underlying mechanisms remain elusive. We hypothesised that a mixture of DDT isomers could exert effects on the liver through pathways instead of classical ERs.

Constitutive androstane receptor activation by 2,4,6-triphenyldioxane-1,3 suppresses the expression of the gluconeogenic genes.

The constitutive androstane receptor (CAR, NR1I3) has a central role in detoxification processes, regulating the expression of a set of genes involved in metabolism. The dual role of NR1I3 as both a xenosensor and as a regulator of endogenous energy metabolism has recently been accepted. Here, we investigated the mechanism of transcriptional regulation of the glucose metabolising genes phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) by the cis isomer of 2,4,6-triphenyldioxane-1,3 (cisTPD), a highly effective NR1I3 activator in rat liver.

Effect of several analogs of 2,4,6-triphenyldioxane-1,3 on CYP2B induction in mouse liver.

2,4,6-Triphenyldioxane-1,3 (TPD) is a highly effective inducer of CYP2В in rats, but not in mice. Several analogs of TPD were synthesized. All substituents were entered into the same position of TPD (R=H, cisTPD and transTPD; R=N(CH(3))(2), transpDMA; R=NO(2), transpNO(2); R=F, transpF; R=OCH(3), transpMeO).

Genetic polymorphism of estrogen metabolizing enzymes in Siberian women with breast cancer.

Allelic variants of cytochrome P450: CYP1A1, CYP1A2, CYP19 (aromatase), and the II-phase enzyme sulfotransferase 1A1 (SULT1A1) genes are associated with a high risk of hormone-dependent cancers. We estimated the frequency of these allelic variants in the female population of the Novosibirsk district and their association with the elevated risk of breast cancer. A DNA bank of patients with gynecologic oncology, patients with breast cancer (n = 335), and healthy women (n = 530) was created, and the following single-nucleotide polymorphisms were examined: CYP1A1 M1 polymorphism, that is, T264-C transition in the 30-noncoding region; CYP1A2*1F polymorphism, that is, C734-A transversion in the CYP1A2 gene; C-T transition (Arg264Cys) in exon 7 of CYP19; and SULT1A1*2 polymorphism, that is, G638-A transition (Arg213His) in the SULT1A1 gene.

Regulation of S100B gene in rat hippocampal CA1 area during long term potentiation.

In the present study we investigated the regulation of S100B expression during tetanization-induced hippocampal long term potentiation, one of the best characterized forms of synaptic plasticity. Tetanization resulted in time-dependent change in S100B gene expression and protein content in hippocampal CA1 area. We analyzed the promoter region of the rat S100B gene and identified response elements for the tumor suppressor p53.