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Article: Identification of BRIP1, NSMCE2, ANAPC7, RAD18 and TTL from chromosome segregation gene set associated with hepatocellular carcinoma.

Sucularli, Ceren

2022 Volume 268-269, Page(s) 28–36

Abstract: Introduction: Hepatocellular carcinoma is one of the most frequent cancers with high mortality rate worldwide.: Methods: TCGA LIHC HTseq counts were analyzed. GSEA was performed with GO BP gene sets. GO analysis was performed with differentially ... ...

Abstract	Introduction: Hepatocellular carcinoma is one of the most frequent cancers with high mortality rate worldwide. Methods: TCGA LIHC HTseq counts were analyzed. GSEA was performed with GO BP gene sets. GO analysis was performed with differentially expressed genes. The subset of genes contributing most of the enrichment result of GO_BP_CHROMOSOME_SEGREGATION of GSEA were identified. Five genes have been selected in this subset of genes for further analysis. A microarray data set, GSE112790, was analyzed as a validation data set. Survival analysis was performed. Results: According to GSEA and GO analysis several gene sets and processes related to chromosome segregation were enriched in LIHC. GO_BP_CHROMOSOME_SEGREGATION gene set from GSEA had the highest size of the genes contributing most of the enrichment. Five genes in this gene set; BRIP1, NSMCE2, ANAPC7, RAD18 and TTL, whose expressions and prognostic values have not been studied in hepatocellular carcinoma in detail, have been selected for further analyses. Expression of these five genes were identified as significantly upregulated in LIHC RNA-seq and HCC microarray data set. Survival analysis showed that high expression of the five genes was associated with poor overall survival in HCC patients. Conclusion: Selected genes were upregulated and had prognostic value in HCC.
MeSH term(s)	Humans ; Carcinoma, Hepatocellular/metabolism ; Liver Neoplasms/metabolism ; Apc7 Subunit, Anaphase-Promoting Complex-Cyclosome ; Chromosome Segregation ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; DNA-Binding Proteins/genetics ; Ubiquitin-Protein Ligases/genetics ; Ligases/genetics ; Ligases/metabolism
Chemical Substances	Apc7 Subunit, Anaphase-Promoting Complex-Cyclosome ; RAD18 protein, human ; DNA-Binding Proteins ; Ubiquitin-Protein Ligases (EC 2.3.2.27) ; NSMCE2 protein, human (EC 6.3.2.-) ; Ligases (EC 6.-)
Language	English
Publishing date	2022-09-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	2599227-2
ISSN	2210-7762
ISSN	2210-7762
DOI	10.1016/j.cancergen.2022.09.003
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Article ; Online: Temporal regulation of gene expression and pathways in chemotherapy-induced senescence in HeLa cervical cancer cell line.

Sucularli, Ceren / Şimay Demir, Yaprak Dilber / Özdemir, Aysun / Ark, Mustafa

Bio Systems

2024 Volume 237, Page(s) 105140

Abstract: Cellular senescence is the state of permanent growth arrest. Chemotherapeutic drugs induce senescence, known as therapy-induced senescence. Although there are studies deciphering processes in senescence, more studies providing detailed information on ... ...

Abstract	Cellular senescence is the state of permanent growth arrest. Chemotherapeutic drugs induce senescence, known as therapy-induced senescence. Although there are studies deciphering processes in senescence, more studies providing detailed information on therapy-induced senescence at the transcriptome level are needed. In order to understand temporal molecular changes of doxorubicin treatment in the course of senescence formation, two data sets from HeLa cells at 16 h and 72 h doxorubicin treatment were analyzed. GO BP enrichment, KEGG pathways and hub genes specific to or shared between 16 h and 72 h doxorubicin treated HeLa cells were identified. Genes functioning in p53 signaling were upregulated only in 16 h, while genes functioning in extracellular matrix organization were upregulated only in 72 h doxorubicin treated HeLa cells. Wound healing genes were gradually upregulated from 16 h to 72 h doxorubicin treatment and metabolic pathways were downregulated at both. ncRNA processing and ribosome biogenesis GO BP terms were enriched in upregulated genes at 16 h, while these terms were enriched in downregulated genes at 72 h senescent HeLa cells. According to our results, genes functioning in p53 signaling may be involved in the induction of senescence, but may not be required to maintain senescence in HeLa cells.
MeSH term(s)	Female ; Humans ; HeLa Cells ; Uterine Cervical Neoplasms/drug therapy ; Uterine Cervical Neoplasms/genetics ; Tumor Suppressor Protein p53/genetics ; Tumor Suppressor Protein p53/pharmacology ; Doxorubicin/pharmacology ; Antineoplastic Agents/therapeutic use ; Gene Expression Regulation ; Cellular Senescence/genetics
Chemical Substances	Tumor Suppressor Protein p53 ; Doxorubicin (80168379AG) ; Antineoplastic Agents
Language	English
Publishing date	2024-02-07
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	186234-0
ISSN	1872-8324 ; 0303-2647
ISSN (online)	1872-8324
ISSN	0303-2647
DOI	10.1016/j.biosystems.2024.105140
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Article ; Online: Acquired immune resistance is associated with interferon signature and modulation of KLF6/c-MYB transcription factors in myeloid leukemia.

Parveen, Mubaida / Karaosmanoglu, Beren / Sucularli, Ceren / Uner, Aysegul / Taskiran, Ekim Z / Esendagli, Gunes

European journal of immunology

2024 Volume 54, Issue 5, Page(s) e2350717

Abstract: Resistance to immunity is associated with the selection of cancer cells with superior capacities to survive inflammatory reactions. Here, we tailored an ex vivo immune selection model for acute myeloid leukemia (AML) and isolated the residual ... ...

Abstract	Resistance to immunity is associated with the selection of cancer cells with superior capacities to survive inflammatory reactions. Here, we tailored an ex vivo immune selection model for acute myeloid leukemia (AML) and isolated the residual subpopulations as "immune-experienced" AML (ieAML) cells. We confirmed that upon surviving the immune reactions, the malignant blasts frequently decelerated proliferation, displayed features of myeloid differentiation and activation, and lost immunogenicity. Transcriptomic analyses revealed a limited number of commonly altered pathways and differentially expressed genes in all ieAML cells derived from distinct parental cell lines. Molecular signatures predominantly associated with interferon and inflammatory cytokine signaling were enriched in the AML cells resisting the T-cell-mediated immune reactions. Moreover, the expression and nuclear localization of the transcription factors c-MYB and KLF6 were noted as the putative markers for immune resistance and identified in subpopulations of AML blasts in the patients' bone marrow aspirates. The immune modulatory capacities of ieAML cells lasted for a restricted period when the immune selection pressure was omitted. In conclusion, myeloid leukemia cells harbor subpopulations that can adapt to the harsh conditions established by immune reactions, and a previous "immune experience" is marked with IFN signature and may pave the way for susceptibility to immune intervention therapies.
MeSH term(s)	Humans ; Kruppel-Like Factor 6/genetics ; Kruppel-Like Factor 6/immunology ; Kruppel-Like Factor 6/metabolism ; Proto-Oncogene Proteins c-myb/genetics ; Proto-Oncogene Proteins c-myb/immunology ; Proto-Oncogene Proteins c-myb/metabolism ; Leukemia, Myeloid, Acute/immunology ; Leukemia, Myeloid, Acute/genetics ; Interferons/immunology ; Interferons/metabolism ; Interferons/genetics ; Female ; Male ; Middle Aged ; Aged ; Cell Line, Tumor ; Adult ; Transcriptome
Chemical Substances	Kruppel-Like Factor 6 ; Proto-Oncogene Proteins c-myb ; KLF6 protein, human ; Interferons (9008-11-1) ; MYB protein, human
Language	English
Publishing date	2024-03-11
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	120108-6
ISSN	1521-4141 ; 0014-2980
ISSN (online)	1521-4141
ISSN	0014-2980
DOI	10.1002/eji.202350717
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Zs.A 489: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Computational prediction and analysis of deleterious cancer associated missense mutations in DYNC1H1.

Sucularli, Ceren / Arslantas, Melda

Molecular and cellular probes

2017 Volume 34, Page(s) 21–29

Abstract: Dynein, cytoplasmic 1, heavy chain 1 (DYNC1H1) gene encodes a subunit of human cytoplasmic dynein complex, which has several crucial functions in the cell, such as intracellular transport of DNA damage proteins and mitotic spindle positioning. Recent ... ...

Abstract	Dynein, cytoplasmic 1, heavy chain 1 (DYNC1H1) gene encodes a subunit of human cytoplasmic dynein complex, which has several crucial functions in the cell, such as intracellular transport of DNA damage proteins and mitotic spindle positioning. Recent studies reported the altered expression of DYNC1H1 in different cancers and DYNC1H1 was suggested to be potential biomarker in colorectal cancers. Previously, DYNC1H1 mutations have been associated with neurodegenerative diseases, however mutations of DYNC1H1 have not been fully investigated in cancers except for different types of pancreatic cancers. In this study we aimed to identify the cancer related mutations in DYNC1H1, which are deleterious for the DYNC1H1 structure and/or function. We investigated 523 cancer related missense mutations in DYNC1H1, which were collected from COSMIC database, to predict the effect of mutations on DYNC1H1 function. Of the 523 mutations, we identified 28 amino acid substitutions, which were predicted to be deleterious by PredictSNP1.0. When we searched for the effect of 28 deleterious mutations on protein stability by MUpro and I-Mutant2.0, we observed that most of the mutations decrease the protein stability. We analyzed the localization of deleterious mutations on primary protein structure and identified that predicted deleterious mutations were mainly located in the motor domain, which is crucial for the DYNC1H1 function. In addition, we detected close positioning of mutated residues in AAA + regions on 3D structure by STRUM and UCSF Chimera. When we searched the mutations in COSMIC database, we observed the occurrence of the mutations in different cancers, which might show the importance of these regions in corresponding cancers. Therefore, our findings provide potential structural and functional mutations and hotspots for DYNC1H1.
MeSH term(s)	Amino Acid Sequence ; Amino Acid Substitution/genetics ; Cytoplasmic Dyneins/genetics ; Humans ; Mutation, Missense/genetics ; Neoplasms/genetics
Chemical Substances	DYNC1H1 protein, human ; Cytoplasmic Dyneins (EC 3.6.4.2)
Language	English
Publishing date	2017
Publishing country	England
Document type	Journal Article
ZDB-ID	639082-1
ISSN	1096-1194 ; 0890-8508
ISSN (online)	1096-1194
ISSN	0890-8508
DOI	10.1016/j.mcp.2017.04.004
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Article: Computational prediction and analysis of deleterious cancer associated missense mutations in DYNC1H1

Sucularli, Ceren / Melda Arslantas

Molecular and cellular probes. 2017 Aug., v. 34

2017

Abstract	Dynein, cytoplasmic 1, heavy chain 1 (DYNC1H1) gene encodes a subunit of human cytoplasmic dynein complex, which has several crucial functions in the cell, such as intracellular transport of DNA damage proteins and mitotic spindle positioning. Recent studies reported the altered expression of DYNC1H1 in different cancers and DYNC1H1 was suggested to be potential biomarker in colorectal cancers. Previously, DYNC1H1 mutations have been associated with neurodegenerative diseases, however mutations of DYNC1H1 have not been fully investigated in cancers except for different types of pancreatic cancers. In this study we aimed to identify the cancer related mutations in DYNC1H1, which are deleterious for the DYNC1H1 structure and/or function. We investigated 523 cancer related missense mutations in DYNC1H1, which were collected from COSMIC database, to predict the effect of mutations on DYNC1H1 function. Of the 523 mutations, we identified 28 amino acid substitutions, which were predicted to be deleterious by PredictSNP1.0. When we searched for the effect of 28 deleterious mutations on protein stability by MUpro and I-Mutant2.0, we observed that most of the mutations decrease the protein stability. We analyzed the localization of deleterious mutations on primary protein structure and identified that predicted deleterious mutations were mainly located in the motor domain, which is crucial for the DYNC1H1 function. In addition, we detected close positioning of mutated residues in AAA + regions on 3D structure by STRUM and UCSF Chimera. When we searched the mutations in COSMIC database, we observed the occurrence of the mutations in different cancers, which might show the importance of these regions in corresponding cancers. Therefore, our findings provide potential structural and functional mutations and hotspots for DYNC1H1.
Keywords	amino acid sequences ; amino acid substitution ; biomarkers ; colorectal neoplasms ; databases ; DNA damage ; dynein ATPase ; genes ; humans ; missense mutation ; mitotic spindle apparatus ; neurodegenerative diseases ; pancreatic neoplasms ; prediction ; proteins
Language	English
Dates of publication	2017-08
Size	p. 21-29.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	639082-1
ISSN	1096-1194 ; 0890-8508
ISSN (online)	1096-1194
ISSN	0890-8508
DOI	10.1016/j.mcp.2017.04.004
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Article ; Online: The implication of ROCK 2 as a potential senotherapeutic target via the suppression of the harmful effects of the SASP: Do senescent cancer cells really engulf the other cells?

Şimay Demir, Yaprak Dilber / Özdemir, Aysun / Sucularlı, Ceren / Benhür, Elifnur / Ark, Mustafa

Cellular signalling

2021 Volume 84, Page(s) 110007

Abstract: Chemotherapy-induced senescent cancer cells secrete several factors in their microenvironment called SASP. Accumulated evidence states that SASP is responsible for some of the harmful effects of chemotherapy such as drug resistance and the induction of ... ...

Abstract	Chemotherapy-induced senescent cancer cells secrete several factors in their microenvironment called SASP. Accumulated evidence states that SASP is responsible for some of the harmful effects of chemotherapy such as drug resistance and the induction of cancer cell proliferation, migration, and invasion. Therefore, to develop senolytic and/or senomorphic drugs, targeting the senescent cells gains importance as a new strategy for preventing the damage that senescent cancer cells cause. In the current work, we evaluated whether Rho/Rho kinase pathway has the potential to be used as a target pathway for the development of senolytic and/or senomorphic drugs in doxorubicin-induced senescent cancer cell lines. We have determined that inhibition of Rho/Rho kinase pathway with CT04 and Y27632 reduced the secretory activity of senescent cancer cells and changed the composition of SASP. Our results indicate that ROCK 2 isoform was responsible for these observed effects on the SASP. In addition, non-senescent cancer cell proliferation and migration accelerated by senescent cells were set back to the pre-induction levels after ROCK inhibition. Moreover, contrary to the previous observations, another important finding of the current work is that senescent HeLa and A549 cells did not engulf the non-senescent HeLa, A549 cells, and non-cancer HUVEC. These results indicate that ROCK inhibitors, in particular ROCK 2 specific inhibitors, have the potential to be developed as novel senomorphic drugs. In addition, we found that all senescent cancer cells do not share the same engulfment ability, and this process should not be generalized.
MeSH term(s)	A549 Cells ; Cell Proliferation ; Cellular Senescence ; HeLa Cells ; Humans ; Neoplasms/drug therapy ; Senotherapeutics
Chemical Substances	Senotherapeutics
Language	English
Publishing date	2021-04-13
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1002702-6
ISSN	1873-3913 ; 0898-6568
ISSN (online)	1873-3913
ISSN	0898-6568
DOI	10.1016/j.cellsig.2021.110007
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Article ; Online: The Expression Profile of Protease Inhibitors in the Airway Epithelial Cells after Allergen (Der p 1) Stimulation.

Karaaslan, Cagatay / Karaguzel, Dilara / Sarac, Basak Ezgi / Sucularli, Ceren / Bilgic, Hayriye Akel / Kalayci, Omer

International archives of allergy and immunology

2021 Volume 183, Issue 1, Page(s) 25–33

Abstract: Background: Airway epithelial cells are constantly exposed to intracellular and extracellular proteases that play a pivotal role in several airway diseases. Dermatophagoides pteronyssinus (Der p) 1 derived from house dust mite has protease activity that ...

Abstract	Background: Airway epithelial cells are constantly exposed to intracellular and extracellular proteases that play a pivotal role in several airway diseases. Dermatophagoides pteronyssinus (Der p) 1 derived from house dust mite has protease activity that causes epithelial barrier defect and inflammatory response. Protease inhibitors released against proteases are involved in the maintenance of homeostasis. A disruption of the balance between proteases and protease inhibitors can lead to distortion of the cellular structures and cellular activities and thus culminate in disease processes. Although the effects of Der p 1 allergen on epithelial barrier integrity and inflammatory response are well-established, its contribution to protease inhibitor production is highly limited. Objective: This study aimed to determine the profile of the protease inhibitor response to Der p 1 allergen in human airway epithelial cells, A549 and BEAS-2B. Methods: Differentiated cells by the air-liquid interface were exposed to Der p 1 with or without Th2 type cytokines (IL-4 and IL-13). Gene expression of protease inhibitors was determined by qPCR at 2 different time points. Results: We found that the effect of allergen exposure on the protease inhibitor profile can vary depending on the antigen concentration, treatment duration, and the presence or absence of type 2 cytokines. Gene expressions of serine protease inhibitor (SERPIN)B3 and SERPINB4 were increased following Th2 cytokine stimulation in both cell types at both time points, whereas SERPINB2 and TFPI-2 expressions were induced by 24-h Der p 1 stimulation in both cells. Conclusions: Our study suggests that Der p 1 exposure of the airway epithelium may have consequences related to its protease activity in the presence as well as in the absence of Th2 cytokines in the microenvironment.
MeSH term(s)	Allergens/immunology ; Antigens, Dermatophagoides/immunology ; Arthropod Proteins/immunology ; Biomarkers ; Cell Line ; Cell Survival ; Cells, Cultured ; Cysteine Endopeptidases/immunology ; Cytokines/genetics ; Cytokines/metabolism ; Epithelial Cells/metabolism ; Gene Expression Regulation ; Humans ; Proteinase Inhibitory Proteins, Secretory/genetics ; Proteinase Inhibitory Proteins, Secretory/metabolism ; Respiratory Mucosa/immunology ; Respiratory Mucosa/metabolism ; Th2 Cells/immunology ; Th2 Cells/metabolism ; Transcriptome
Chemical Substances	Allergens ; Antigens, Dermatophagoides ; Arthropod Proteins ; Biomarkers ; Cytokines ; Proteinase Inhibitory Proteins, Secretory ; Cysteine Endopeptidases (EC 3.4.22.-) ; Dermatophagoides pteronyssinus antigen p 1 (EC 3.4.22.-)
Language	English
Publishing date	2021-08-20
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1108932-5
ISSN	1423-0097 ; 1018-2438
ISSN (online)	1423-0097
ISSN	1018-2438
DOI	10.1159/000518170
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Article ; Online: Genetic Analysis of

Durmaz, Ceren Damla / Karabulut, Halil Gürhan / Saka, Meram Can / Sucularlı, Ceren / Gümüş Akay, Güvem / Atbaşoğlu, Cem / Ilgın Ruhi, Hatice

Balkan medical journal

2022 Volume 39, Issue 6, Page(s) 422–428

Abstract: Background: RASD1: Aims: To investigate the association of : Study design: A case-control study.: Methods: We performed targeted sequencing for the two exons, single intron, and untranslated regions of : Results: Two rare variants, : ... ...

Abstract	Background: RASD1 Aims: To investigate the association of Study design: A case-control study. Methods: We performed targeted sequencing for the two exons, single intron, and untranslated regions of Results: Two rare variants, Conclusion: Our findings suggest that rare variants of
MeSH term(s)	Humans ; Schizophrenia/genetics ; ras Proteins/genetics ; ras Proteins/metabolism ; Case-Control Studies ; Exons ; Genetic Testing ; Adaptor Proteins, Signal Transducing/genetics ; Adaptor Proteins, Signal Transducing/metabolism
Chemical Substances	ras Proteins (EC 3.6.5.2) ; RASD1 protein, human ; NOS1AP protein, human ; Adaptor Proteins, Signal Transducing
Language	English
Publishing date	2022-10-28
Publishing country	Turkey
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2612982-6
ISSN	2146-3131 ; 2146-3131
ISSN (online)	2146-3131
ISSN	2146-3131
DOI	10.4274/balkanmedj.galenos.2022.2022-5-90
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Article: High-throughput gene expression analysis identifies p53-dependent and -independent pathways contributing to the adrenocortical dysplasia (acd) phenotype

Sucularli, Ceren / Thomas, Peedikayil / Kocak, Hande / White, James S / O'Connor, Bridget C / Keegan, Catherine E

Gene. 2018,

2018

Abstract: In mammalian cells TPP1, encoded by the Acd gene, is a key component of the shelterin complex, which is required for telomere length maintenance and telomere protection. In mice, a hypomorphic mutation in Acd causes the adrenocortical dysplasia (acd) ... ...

Abstract	In mammalian cells TPP1, encoded by the Acd gene, is a key component of the shelterin complex, which is required for telomere length maintenance and telomere protection. In mice, a hypomorphic mutation in Acd causes the adrenocortical dysplasia (acd) phenotype, which includes limb and body axis anomalies, and perinatal lethality. p53 deficiency partially rescues limb and body axis anomalies in acd mutant embryos, but not perinatal lethality, implicating p53-independent mechanisms in the acd phenotype. Loss of function of most shelterin proteins results in early embryonic lethality. Thus, study of the hypomorphic acd allele provides a unique opportunity to understand telomere dysfunction at an organismal level. The aim of this study was to identify transcriptome alterations in acd mutant and acd, p53 double mutant embryos to understand the p53-dependent and –independent factors that contribute to the mutant phenotypes in the context of the whole organism. Genes involved in developmental processes, cell cycle, metabolic pathways, tight junctions, axon guidance and signaling pathways were regulated by p53-driven mechanisms in acd mutant embryos, while genes functioning in immune response, and RNA processing were altered independently of p53 in acd, p53 double mutant embryos. To our best of knowledge, this is the first study revealing detailed transcriptomic alterations, reflecting novel p53-dependent and -independent pathways contributing to the acd phenotype. Our data confirm the importance of cell cycle and DNA repair pathways, and suggest novel links between telomere dysfunction and immune system regulation and the splicing machinery. Given the broad applicability of telomere maintenance in growth, development, and genome stability, our data will also provide a rich resource for others studying telomere maintenance and DNA damage responses in mammalian model systems.
Keywords	DNA damage ; DNA repair ; RNA ; alleles ; axons ; biochemical pathways ; cell cycle ; death ; gene expression ; immune response ; immune system ; mice ; models ; mutants ; mutation ; phenotype ; proteins ; signal transduction ; telomeres ; tight junctions ; transcriptome ; transcriptomics
Language	English
Publishing place	Elsevier B.V.
Document type	Article
Note	Pre-press version
ZDB-ID	391792-7
ISSN	1879-0038 ; 0378-1119
ISSN (online)	1879-0038
ISSN	0378-1119
DOI	10.1016/j.gene.2018.09.002
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Article ; Online: CHRNA5 belongs to the secondary estrogen signaling network exhibiting prognostic significance in breast cancer.

Shehwana, Huma / Keskus, Ayse G / Ozdemir, Sila E / Acikgöz, Azer A / Biyik-Sit, Rumeysa / Cagnan, Ilgin / Gunes, Damla / Jahja, Ermira / Cingir-Koker, Sahika / Olmezer, Gizem / Sucularli, Ceren / Konu, Ozlen

Cellular oncology (Dordrecht)

2021 Volume 44, Issue 2, Page(s) 453–472

Abstract: Purpose: Cholinergic signals can be important modulators of cellular signaling in cancer. We recently have shown that knockdown of nicotinic acetylcholine receptor subunit alpha 5, CHRNA5, diminishes the proliferative potential of breast cancer cells. ... ...

Abstract	Purpose: Cholinergic signals can be important modulators of cellular signaling in cancer. We recently have shown that knockdown of nicotinic acetylcholine receptor subunit alpha 5, CHRNA5, diminishes the proliferative potential of breast cancer cells. However, modulation of CHRNA5 expression in the context of estrogen signaling and its prognostic implications in breast cancer remained unexplored. Methods: Meta-analyses of large breast cancer microarray cohorts were used to evaluate the association of CHRNA5 expression with estrogen (E2) treatment, estrogen receptor (ER) status and patient prognosis. The results were validated through RT-qPCR analyses of multiple E2 treated cell lines, CHRNA5 depleted MCF7 cells and across a breast cancer patient cDNA panel. We also calculated a predicted secondary (PS) score representing direct/indirect induction of gene expression by E2 based on a public dataset (GSE8597). Co-expression analysis was performed using a weighted gene co-expression network analysis (WGCNA) pipeline. Multiple other publicly available datasets such as CCLE, COSMIC and TCGA were also analyzed. Results: Herein we found that CHRNA5 expression was induced by E2 in a dose- and time-dependent manner in breast cancer cell lines. ER Conclusion: Our findings strongly associate increased expression of CHRNA5 and its co-expression network with secondary E2 signaling and a worse prognosis in breast cancer.
MeSH term(s)	Breast Neoplasms/genetics ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Cell Line, Tumor ; Estrogen Receptor alpha/metabolism ; Estrogens/metabolism ; Estrogens/pharmacology ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Gene Regulatory Networks ; Humans ; Nerve Tissue Proteins/genetics ; Nerve Tissue Proteins/metabolism ; Prognosis ; RNA, Small Interfering/metabolism ; Receptors, Estrogen/metabolism ; Receptors, Nicotinic/genetics ; Receptors, Nicotinic/metabolism ; Signal Transduction/drug effects ; Transcription Factors/metabolism ; Up-Regulation/drug effects ; Up-Regulation/genetics
Chemical Substances	CHRNA5 protein, human ; Estrogen Receptor alpha ; Estrogens ; Nerve Tissue Proteins ; RNA, Small Interfering ; Receptors, Estrogen ; Receptors, Nicotinic ; Transcription Factors
Language	English
Publishing date	2021-01-19
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2595109-9
ISSN	2211-3436 ; 1875-8606 ; 2211-3428
ISSN (online)	2211-3436
ISSN	1875-8606 ; 2211-3428
DOI	10.1007/s13402-020-00581-x
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