Jean-Bosco Tagne

Boston University | BU · Department of Medicine

Background MicroRNAs are noncoding RNA molecules of ~ 22 nucleotides with diagnostic and therapeutic action [Curr Drug Targets, 2015. 16(12): p. 1381-403], affecting the expression of mRNAs involved in invasion, migration, and development [Oncotarget, 2015. 6(9): p. 6472-98, Cancer Manag Res, 2014. 6: p. 205-16]. miR-200c is part of the miR-200c/14...

The function of most long noncoding RNAs (lncRNAs) is unknown. However, recent studies reveal important roles of lncRNAs in regulating cancer-related pathways. Human antisense lncRNA-NKX2-1-AS1 partially overlaps the NKX2-1/TTF1 gene within chromosomal region 14q13.3. Amplification of this region and/or differential expression of genes therein are...

Distinct members of the Ets family of transcription factors act as positive or negative regulators of genes involved in cellular proliferation, development, and tumorigenesis. In human lung cancer, increased ETS1 expression is associated with poor prognosis and metastasis. We tested whether ETS1 contributes to lung tumorigenesis by binding to Twist...

The transcription factor NK2 homeobox 1 (Nkx2-1) plays essential roles in epithelial cell proliferation and differentiation in mouse and human lung development and tumorigenesis. A better understanding of genes and pathways downstream of Nkx2-1 will clarify the multiple roles of this critical lung factor. Nkx2-1 regulates directly or indirectly num...

The vasculopathy of sickle cell disease (SCD), characterized by a chronic hemolytic anemia, endothelial dysfunction and recurrent vasoocclusive events, underlies most of the clinical complications. Recent work has suggested that hydroxyurea (HU) enhances endothelial nitric oxide (NO) production and reduces adhesion molecule expression which may con...

The Grainyhead family of transcription factors controls morphogenesis and differentiation of epithelial cell layers in multicellular organisms by regulating cell junction- and proliferation-related genes. Grainyhead-like 2 (Grhl2) is expressed in developing mouse lung epithelium and is required for normal lung organogenesis. The specific epithelial...

The homeodomain transcription factor Nkx2-1 is essential for normal lung development and homeostasis. In lung tumors, it is considered a lineage survival oncogene and prognostic factor depending on its expression levels. The target genes directly bound by Nkx2-1, that could be the primary effectors of its functions in the different cellular context...

(a). Target genes at E11.5 (log(2) >0.75, p≤0.001). (b) Target genes at E19.5 (log(2) >0.75, p≤0.001). (DOC)

Nkx2-1 target genes expressed in lung development and correlated to NKX2-1 levels in human lung tumor datasets. (DOC)

Relative expression of selected Nkx2-1 target genes in E12 and E18 developing mouse lung extracted from the expression microarray dataset GEO series GSE 10889 (27). (TIF)

Comparison of three commercial Nkx2-1 antibodies. Western blot experiments were performed using MLE15 lung epithelial cell protein extracts. Nkx2-1 rabbit polyclonal antibody (EMD-Millipore-Upstate), rabbit monoclonal antibody (Abcam) and mouse monoclonal antibody (LabVision, Fisher Scientific) detect a strong band between 40–45 kD (upper black arr...

Genes bound and regulated by Nkx2-1 in human fetal lung epithelial cells. (DOC)

PCR and qPCR Oligonucleotide sequences. (DOC)

Genome-wide patterns of Nkx2-1 binding. Location of Nkx2-1 binding in all mouse chromosomes in E11.5 (red) and E19.5 (green) lungs. X axis (chromosomal location), y axis (binding signal intensity). (TIF)

Nkx2-1 binding patterns to selected target genes in lung development. Binding profiles of Nkx2-1 to newly identified target genes (left panel). Chromatin immunoprecipitation-qPCR validation of Nkx2-1 binding to target genes (right panel). IP DNA from E11.5 and E19.5 lungs, input and IgG immunoprecipitated control were used in qPCR analyses. Oligonu...

Nkx2-1 levels in human lung tumors significantly correlate with expression of developmental Nkx2-1 target genes. Additional heatmaps of human lung tumor genes identified in GSE 12667 dataset showing gene expression levels of the human homologues of Nkx2-1 target genes identified in mouse lung development at E11.5 (upper panel) and E19.5 (lower pane...

Nkx2-1 target genes genes included in Cancer pathways identified by IPA. (DOC)

(a) E11.5 overrepresented biological processes identified by EASE analysis p<0.05. (b) E19.5 overrepresented biological processes identified by EASE analysis (p<0.05). (DOC)

Overrepresented canonical pathways identified by Ingenuity Pathway Analysis Software. (DOC)

Unlabelled: Dacarbazine (DAC) is an anticancer drug that has been used to treat various types of cancers. The aim of the current study was to test whether there is an increased efficacy of DAC as a nanoemulsion on reducing tumor size in an epidermoid carcinoma xenograft mouse model. Tumors were induced in 5-week-old nude mice by subcutaneous injec...

Epigenetic regulation of transcription plays an important role in cell-specific gene expression by altering chromatin structure and access of transcriptional regulators to DNA binding sites. Surfactant protein B (Sftpb) is a developmentally regulated lung epithelial gene critical for lung function. Thyroid transcription factor 1 (Nkx2-1) regulates...

This article reports on the preparation of a water-soluble nanoemulsion of the highly lipid-soluble drug Dacarbazine (DAC). In addition, relative to suspensions of DAC, the nanoemulsion preparation demonstrated a lower zeta-potential (decreased negative charge, less anionic and more cationic) which has previously been associated with influencing dr...

This paper reports on the preparation of a water-soluble nanoemulsion of the highly lipid-soluble drug tamoxifen (TAM). In addition, relative to a suspension of TAM, the nanoemulsion preparation demonstrated a greater zeta potential (increased negative charge) which has previously been associated with increasing drug/membrane permeability. This stu...

Neuroblastoma, the most common form of childhood cancer, may arise from a biochemical block of cellular differentiation and a resultant continuation of a proliferative state. Neuroblastoma often spontaneously reverts by undergoing partial differentiation and ultimate degeneration and may be associated with the generation of reactive oxygen species...

Failure of cells to respond to DNA damage is a primary event associated with mutagenesis and environmental toxicity. To map the transcriptional network controlling the damage response, we measured genomewide binding locations for 30 damage-related transcription factors (TFs) after exposure of yeast to methyl-methanesulfonate (MMS). The resulting 52...

In Saccharomyces cerevisiae, glucose depletion causes a profound alteration in metabolism, mediated in part by global transcriptional changes. Many of the transcription factors that regulate these changes act combinatorially. We have analyzed combinatorial regulation by Adr1 and Cat8, two transcription factors that act during glucose depletion, by...

DNA-binding transcriptional regulators interpret the genome's regulatory code by binding to specific sequences to induce or repress gene expression. Comparative genomics has recently been used to identify potential cis-regulatory sequences within the yeast genome on the basis of phylogenetic conservation, but this information alone does not reveal...

The patterns of transcription and translation of the ribosomal protein L32 (Rpl32) mRNA differ greatly in adult testis and somatic tissues. Northern blots reveal that the levels of Rpl32 mRNA are four- to five-fold higher in prepubertal and adult testes, and purified pachytene spermatocytes and round spermatids than in a variety of nongrowing adult...

We have determined how most of the transcriptional regulators encoded in the eukaryote Saccharomyces cerevisiaeassociate with genes across the genome in living cells. Just as maps of metabolic networks describe the potential pathways that may be used by a cell to accomplish metabolic processes, this network of regulator-gene interactions describes...

METHODS Epitope Tagging of Strains Regulators were tagged by inserting multiple copies of the Myc epitope coding sequence into the normal chomosomal loci of these genes. The plasmid pWZV88 (1) was used as a template to generate PCR products containing the Myc epitope coding sequence and a selectable marker (TRP) flanked by homologous regions design...

Thesis (M.S.)--University of Massachusetts Boston, 2002.