scholarly journals Characterization of interleukin-1β mRNA expression in chicken macrophages in response to avian reovirus

2008 ◽  
Vol 89 (4) ◽  
pp. 1059-1068 ◽  
Author(s):  
Yung Fu Wu ◽  
Hung Jen Liu ◽  
Jui Huang Shien ◽  
Shiow Her Chiou ◽  
Long Huw Lee
Keyword(s):  
Mrna Expression ◽  
Expression Pattern ◽  
Interleukin 1 ◽  
Expression Patterns ◽  
Protein Translation ◽  
Post Inoculation ◽  
Avian Reovirus ◽  
Viral Particles ◽  
Rna And Protein Synthesis

Inhibitors of viral disassembly or RNA and protein synthesis, viral disassembly intermediates (infectious subviral particles, ISVP), binary ethylenimine-inactivated virions, and viral particles lacking genomic double-stranded (ds) RNA (empty particles) were used to assess the expression of interleukin-1β (IL-1β) mRNA in chicken (chIL-1β) macrophages in response to avian reovirus. The results demonstrate that two distinct expression patterns of chIL-1β mRNA mediated by different steps in viral replication were found. Viral disassembly was required for the induction of a rapid, transient expression pattern of chIL-1β mRNA that was rapidly induced at 30 min, with maximal levels reached by 2 h, and fell to a low level within 6 h post-inoculation, while viral RNA synthesis rather than protein translation, which was subsequent to membrane penetration, was required to induce a stable, sustained expression pattern of chIL-1β mRNA that occurred at and after 6 h post-inoculation. In addition, the induction of chIL-1β mRNA expression by the empty particles and ISVP was extremely weak, compared with the active dsRNA+ virions or binary ethylenimine-inactivated virions, suggesting that the presence of dsRNA, even if transcriptionally inactive, may be an important factor in this response.

MicroRNAs in Normal Human Terminal Granulocytic Differentiation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1463-1463
Author(s):  
Su Ming Sun ◽  
Menno K Dijkstra ◽  
André C Bijkerk ◽  
Rik Brooijmans ◽  
Peter J Valk ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Mrna Expression ◽  
Expression Pattern ◽  
Mirna Expression ◽  
Expression Patterns ◽  
Granulocytic Differentiation ◽  
Expression Levels ◽  
Mirna Expression Pattern ◽  
Normal Human

Abstract Abstract 1463 Poster Board I-486 Normal human myelopoiesis is a complex biological process, where the balance between cell proliferation, differentiation and apoptosis is tightly regulated by a transcriptional program that results in the production of appropriate numbers of circulating mature myeloid cells. MicroRNAs (miRNAs) are small non-coding RNAs of 18∼25 nt that can affect cellular protein levels. Several studies show specific miRNA expression patterns in different subtypes of myeloid malignancies, however only limited data is available on miRNA expression patterns during normal myeloid differentiation of primary human cells. We set out to characterize miRNA expression patterns in the different stages of granulocytic differentiation in two models. First myeloblast, promyelocytes, metamyelocytes and granulocytes from normal human bone marrow were cell-sorted with flow cytometry using the markers CD10, CD11, CD34, CD36, CD45 and CD117. Second, CD34+ cells from primary human fetal livers were differentiated in vitro towards neutrophils. MiRNA expression levels were determined at different time points (day 0, 3 and 10), representing different stages of granulocytic differentiation. MiRNA expression was measured using the qPCR platform, containing 365 miRNAs, from Applied Biosystems. To identify potential miRNA target genes, we performed mRNA expression profiling in the latter in vitro differentiation. The negative correlations between miRNA and mRNA expression were identified and integrated with a target prediction database (Targetscan). The miRNA profiling showed that approximately 70% of the 365 miRNAs analyzed, were expressed during granulocytic differentiation and that the miRNA expression pattern during this process change significantly in both models. Principal component analysis showed clear separation of the different subsets of granulopoiesis based on the miRNA expression. We determined the differentially expressed miRNAs between the various subsets using ANOVA with a P value <0.05, after correction for multiple testing. We found 24 miRNAs to be differentially upregulated in the both models. The top 5 upregulated miRNA, with the highest fold change in granulocytes as compared to myeloblasts, were miR-223, miR-145, miR-148, miR-24 and miR-23a. We identified 27 miRNAs that were downregulated, the top 5 were of miR-10a, miR-196a, miR-130a, miR-135a and miR-125b. Concomitant miRNA and mRNA expression analysis of the in vitro model with the Targetscan database, demonstrates a potential regulatory role for these miRNAs in various processes, such as cell proliferation, apoptosis and cell cycle regulation. For example, miR-130a, miR-20b and miR-191, miR-301 expression levels were negatively correlated with E2F2 and SOX4 respectively. Furthermore, MAPK1 levels correlated inversely with miR-17-5p, miR-130a, miR-181b, miR-181d and miR-20b. We observed potential regulation of BCL2L11 by miR-10a, miR-10b and CDK6 by miR-148a, miR-148b, miR-191 and miR-21, as well as CHEK1 by the miR-15a and miR-16, LATS2 by miR-142-3p and CCND3 by miR-133a. In addition we also identified myeloid specific genes to be potentially regulated by miRNAs such as CEBPA by miR-181b, KIT by miR-148a, miR-148b and miR-301 and RUNX3 by miR-301. This is the first comprehensive study of miRNA expression in normal human granulocytic differentiation. We show in two models that the miRNA expression pattern changes during granulocytic differentiation. miRNA-mRNA analyses suggest involvement of miRNAs in regulation of important cellular processes during granulocytic differentiation. Experimental validations of several candidate targets as well as functional studies are currently ongoing. Disclosures No relevant conflicts of interest to declare.

scholarly journals IL-1-conferred gene expression pattern in ERα+ BCa and AR+ PCa cells is intrinsic to ERα- BCa and AR- PCa cells and promotes cell survival

2020 ◽  
Author(s):  
Afshan F. Nawas ◽  
Mohammed Kanchwala ◽  
Shayna E. Thomas-Jardin ◽  
Haley Dahl ◽  
Kelly Daescu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Pattern ◽  
Cell Lines ◽  
Hormone Receptor ◽  
Interleukin 1 ◽  
Expression Patterns ◽  
Gene Expression Pattern ◽  
Treatment Resistance ◽  
Rna Seq ◽  
Data Set

Abstract Background: Breast (BCa) and prostate (PCa) cancers are hormone receptor (HR)-driven cancers. Thus, BCa and PCa patients are given therapies that reduce hormone levels or directly block HR activity; but most patients eventually develop treatment resistance. We have previously reported that interleukin-1 (IL-1) inflammatory cytokine downregulates ERα and AR mRNA in HR-positive (HR+) BCa and PCa cell lines, yet the cells can remain viable. Additionally, we identified pro-survival proteins and processes upregulated by IL-1 in HR+ BCa and PCa cells, that are basally high in HR- BCa and PCa cells. Therefore, we hypothesize that IL-1 confers a conserved gene expression pattern in HR+ BCa and PCa cells that mimics conserved basal gene expression patterns in HR- BCa and PCa cells to promote HR-independent survival and tumorigenicity. Methods: We performed RNA sequencing (RNA-seq) for HR+ BCa and PCa cell lines exposed to IL-1 and for untreated HR- BCa and PCa cell lines. We confirmed expression patterns of select genes by RT-qPCR and used siRNA and/or drug inhibition to silence select genes in the BCa and PCa cell lines. Finally, we performed Ingenuity Pathway Analysis (IPA) and used the gene ontology web-based tool, GOrilla, to identify signaling pathways encoded by our RNA-seq data set. Results: We identified 350 genes in common between BCa and PCa cells that are induced or repressed by IL-1 in HR+ cells that are, respectively, basally high or low in HR- cells. Among these genes, we identified Sequestome-1 (SQSTM1/p62) and SRY (Sex-Determining Region Y)-Box 9 (SOX9) to be essential for survival of HR- BCa and PCa cell lines. Analysis of publicly available data indicates that p62 and SOX9 expression are elevated in HR-independent BCa and PCa sublines generated in vitro, suggesting that p62 and SOX9 have a role in acquired hormone receptor independence and treatment resistance. We also assessed HR- cell line viability in response to the p62-targeting drug, verteporfin, and found that verteporfin is cytotoxic for HR- cell lines. Conclusions: Our 350 gene set can be used to identify novel therapeutic targets and/or biomarkers conserved among acquired (e.g. due to inflammation) or intrinsic HR-independent BCa and PCa.

scholarly journals IL-1-conferred gene expression pattern in ERα+ BCa and AR+ PCa cells is intrinsic to ERα- BCa and AR- PCa cells and promotes cell survival

2019 ◽  
Author(s):  
Afshan F. Nawas ◽  
Mohammed Kanchwala ◽  
Shayna E. Thomas-Jardin ◽  
Haley Dahl ◽  
Kelly Daescu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Pattern ◽  
Cell Lines ◽  
Interleukin 1 ◽  
Expression Patterns ◽  
Gene Expression Pattern ◽  
Treatment Resistance ◽  
Rna Seq ◽  
Drug Inhibition

Abstract Background: Breast (BCa) and prostate (PCa) cancers are hormone receptor (HR)-driven cancers. Thus, BCa and PCa patients are given therapies that reduce hormone levels or directly blocks HR activity; but most patients eventually develop treatment resistance. We have previously reported that interleukin-1 (IL-1) inflammatory cytokine downregulates ER𝛼 and AR mRNA in HR-positive (HR+) BCa and PCa cell lines, yet the cells can remain viable. Additionally, we identified pro-survival proteins and processes upregulated by IL-1 in HR+ BCa and PCa cells, that are basally high in HR- BCa and PCa cells. Therefore, we hypothesize that IL-1 confers a conserved gene expression pattern in HR+ BCa and PCa cells that mimics conserved basal gene expression patterns in HR- BCa and PCa cells to promote HR-independent survival and tumorigenicity.Methods: We performed RNA sequencing (RNA-seq) for HR+ BCa and PCa cell lines exposed to IL-1 and for untreated HR- BCa and PCa cell lines. We confirmed expression patterns of select genes by RT-qPCR and used siRNA and/or drug inhibition to silence select genes in HR- BCa cell lines. Finally, we performed Ingenuity Pathway Analysis (IPA) to identify signaling pathways encoded by our RNA-seq data set.Results: We identified 350 genes in common between BCa and PCa cells that are induced or repressed by IL-1 in HR+ cells that are, respectively, basally high or low in HR- cells. Among these genes, we identified Sequestome-1 (SQSTM1/p62) and SRY (Sex-Determining Region Y)-Box 9 (SOX9) to be essential for survival of HR- BCa and PCa cell lines. Analysis of publicly available data indicates that p62 and SOX9 expression are elevated in HR-independent BCa and PCa sublines generated in vitro, suggesting that p62 and SOX9 have a role in acquired treatment resistance. We also assessed HR- cell line viability in response to the p62-targeting drug, verteporfin, and found that verteporfin is cytotoxic for HR- cell lines. Conclusions: Our 350 gene set can be used to identify novel therapeutic targets and/or biomarkers conserved among acquired (e.g. due to inflammation) or intrinsic HR-independent BCa and PCa.

scholarly journals IL-1-conferred gene expression pattern in ERα+ BCa and AR+ PCa cells is intrinsic to ERα− BCa and AR− PCa cells and promotes cell survival

2019 ◽  
Author(s):  
Afshan F. Nawas ◽  
Mohammed Kanchwala ◽  
Shayna E. Thomas-Jardin ◽  
Haley Dahl ◽  
Kelly Daescu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Pattern ◽  
Cell Lines ◽  
Interleukin 1 ◽  
Expression Patterns ◽  
Gene Expression Pattern ◽  
Treatment Resistance ◽  
Rna Seq ◽  
Data Set

ABSTRACTBackgroundBreast (BCa) and prostate (PCa) cancers are hormone receptor (HR)-driven cancers. Thus, BCa and PCa patients are given therapies that reduce hormone levels or directly blocks HR activity; but most patients eventually develop treatment resistance. We have previously reported that interleukin-1 (IL-1) inflammatory cytokine downregulates ERα and AR mRNA in HR-positive (HR+) BCa and PCa cell lines, yet the cells can remain viable. Additionally, we identified pro-survival proteins and processes upregulated by IL-1 in HR+ BCa and PCa cells, that are basally high in HR− BCa and PCa cells. Therefore, we hypothesize that IL-1 confers a conserved gene expression pattern in HR+ BCa and PCa cells that mimics conserved basal gene expression patterns in HR− BCa and PCa cells to promote HR-independent survival and tumorigenicity.MethodsWe performed RNA sequencing (RNA-seq) for HR+ BCa and PCa cell lines exposed to IL-1 and for untreated HR− BCa and PCa cell lines. We confirmed expression patterns of select genes by RT-qPCR and used siRNA and/or drug inhibition to silence select genes in HR− BCa cell lines. Finally, we performed Ingenuity Pathway Analysis (IPA) to identify signaling pathways encoded by our RNA-seq data set.ResultsWe identified 350 genes in common between BCa and PCa cells that are induced or repressed by IL-1 in HR+ cells that are, respectively, basally high or low in HR− cells. Among these genes, we identified Sequestome-1 (SQSTM1/p62) and SRY (Sex-Determining Region Y)-Box 9 (SOX9) to be essential for survival of HR− BCa and PCa cell lines. Analysis of publicly available data indicates that p62 and SOX9 expression are elevated in HR-independent BCa and PCa sublines generated in vitro, suggesting that p62 and SOX9 have a role in acquired treatment resistance. We also assessed HR− cell line viability in response to the p62-targeting drug, verteporfin, and found that verteporfin is cytotoxic for HR− cell lines.ConclusionsOur 350 gene set can be used to identify novel therapeutic targets and/or biomarkers conserved among acquired (e.g. due to inflammation) or intrinsic HR-independent BCa and PCa.

scholarly journals Characterization of an alternatively spliced AATYK mRNA: Expression pattern of AATYK in the brain and neuronal cells

Oncogene ◽  
2001 ◽  
Vol 20 (9) ◽  
pp. 1015-1021 ◽  
Author(s):  
Stacey J Baker ◽  
Rachel Sumerson ◽  
C Damodar Reddy ◽  
Albert S Berrebi ◽  
Daniel C Flynn ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Expression Pattern ◽  
Neuronal Cells ◽  
Mrna Expression Pattern ◽  
Alternatively Spliced ◽  
The Brain

scholarly journals IL-1-conferred gene expression pattern in ERα+ BCa and AR+ PCa cells is intrinsic to ERα- BCa and AR- PCa cells and promotes cell survival

2019 ◽  
Author(s):  
Afshan F. Nawas ◽  
Mohammed Kanchwala ◽  
Shayna E. Thomas-Jardin ◽  
Haley Dahl ◽  
Kelly Daescu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Pattern ◽  
Cell Lines ◽  
Hormone Receptor ◽  
Interleukin 1 ◽  
Expression Patterns ◽  
Gene Expression Pattern ◽  
Treatment Resistance ◽  
Rna Seq

Abstract Background Breast (BCa) and prostate (PCa) cancers are hormone receptor (HR)-driven cancers. Thus, BCa and PCa patients are given therapies that reduce hormone levels or directly blocks HR activity; but most patients eventually develop treatment resistance. We have previously reported that interleukin-1 (IL-1) inflammatory cytokine downregulates ERα and AR mRNA in HR-positive (HR+) BCa and PCa cell lines, yet the cells can remain viable. Additionally, we identified pro-survival proteins and processes upregulated by IL-1 in HR+ BCa and PCa cells, that are basally high in HR- BCa and PCa cells. Therefore, we hypothesize that IL-1 confers a conserved gene expression pattern in HR+ BCa and PCa cells that mimics conserved basal gene expression patterns in HR- BCa and PCa cells to promote HR-independent survival and tumorigenicity.Methods We performed RNA sequencing (RNA-seq) for HR+ BCa and PCa cell lines exposed to IL-1 and for untreated HR- BCa and PCa cell lines. We confirmed expression patterns of select genes by RT-qPCR and used siRNA and/or drug inhibition to silence select genes in HR- BCa cell lines. Finally, we performed Ingenuity Pathway Analysis (IPA) and used the gene ontology web-based tool, GOrilla, to identify signaling pathways encoded by our RNA-seq data set.Results We identified 350 genes in common between BCa and PCa cells that are induced or repressed by IL-1 in HR+ cells that are, respectively, basally high or low in HR- cells. Among these genes, we identified Sequestome-1 (SQSTM1/p62) and SRY (Sex-Determining Region Y)-Box 9 (SOX9 ) to be essential for survival of HR- BCa and PCa cell lines. Analysis of publicly available data indicates that p62 and SOX9 expression are elevated in HR-independent BCa and PCa sublines generated in vitro, suggesting that p62 and SOX9 have a role in acquired hormone receptor independence and treatment resistance. We also assessed HR- cell line viability in response to the p62-targeting drug, verteporfin, and found that verteporfin is cytotoxic for HR- cell lines. Conclusions Our 350 gene set can be used to identify novel therapeutic targets and/or biomarkers conserved among acquired (e.g. due to inflammation) or intrinsic HR-independent BCa and PCa.

Sign in / Sign up

Export Citation Format

Share Document