Gene Expression 16(4) Abstracts

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Gene Expression, Vol. 16, pp. 155–162, 2015
1052-2166/13 $90.00
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DOI: http://dx.doi.org/10.3727/105221615X14399878166078
E-ISSN 1555-3884
Copyright ©
2015 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Review

Role of Noncoding RNAs as Biomarker and Therapeutic Targets for Liver Fibrosis

Kun-Yu Teng and Kalpana Ghoshal

Department of Pathology, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA

Noncoding RNAs (ncRNAs) including microRNAs (miRNAs) regulate gene expression at the posttranscriptional level, whereas long coding RNAs (lncRNAs) modulate gene expression both at transcriptional and posttranscriptional levels in mammals. Accumulated evidence demonstrates the widespread aberrations in ncRNA expression associated with almost all types of liver disease. However, the role of ncRNAs in liver fibrosis is poorly understood. Liver fibrosis is the process of excessive accumulation of extracellular matrix (ECM) proteins in the liver that lead to organ dysfunction and tumorigenesis. In this review, we summarize the current knowledge on the role of ncRNAs in promoting or repressing liver fibrosis caused by nonviral agents, potential use of circulating miRNAs as biomarkers of liver fibrosis, and therapeutic approaches to treat liver fibrosis by targeting the dysregulated miRNAs.

Key words: Liver fibrosis; Noncoding RNAs (ncRNAs); MicroRNAs (miRNAs); Long noncoding RNAs (lncRNAs)

Address correspondence to Kalpana Ghoshal, Department of Pathology, Comprehensive Cancer Center, The Ohio State University, College of Medicine 646C MRF, 420 W. 12th Avenue, Columbus, OH 43210, USA. Tel: 614-292-8865; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Gene Expression, Vol. 16, pp. 163–168, 2015
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DOI: http://dx.doi.org/10.3727/105221615X14399878166113
E-ISSN 1555-3884
Copyright ©
2015 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Review

GATA3 in Breast Cancer: Tumor Suppressor or Oncogene?

Motoki Takaku,* Sara A. Grimm,† and Paul A. Wade*

*Epigenetics and Stem Cell Biology Laboratory, National Institute of Environmental Health Science, Research Triangle Park, NC, USA
†Integrated Bioinformatics, National Institute of Environmental Health Science, Research Triangle Park, NC, USA

GATA3 is a highly conserved, essential transcription factor expressed in a number of tissues, including the mammary gland. GATA3 expression is required for normal development of the mammary gland where it is estimated to be the most abundant transcription factor in luminal epithelial cells. In breast cancer, GATA3 expression is highly correlated with the luminal transcriptional program. Recent genomic analysis of human breast cancers has revealed high-frequency mutation in GATA3 in luminal tumors, suggesting “driver” function(s). Here we discuss mutation of GATA3 in breast cancer and the potential mechanism(s) by which mutation may lead to a growth advantage in cancer.

Key words: Oncogene; GATA3; Tumor suppressor; Breast cancer

Address correspondence to Paul A. Wade, National Institute of Environmental Health Science, 111 TW Alexander Drive, Mail Drop D4-04, Research Triangle Park, NC 27709, USA. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Gene Expression, Vol. 16, pp. 169–175, 2015
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DOI: http://dx.doi.org/10.3727/105221615X14399878166159
E-ISSN 1555-3884
Copyright ©
2015 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Short Report

Cord Blood-Derived Quiescent CD34+
Cells Are More Transcriptionally Matched to AML Blasts Than Cytokine-Induced Normal Human Hematopoietic CD34+ Cells

Chinmay Munje,*,Robert K. Hills,* Anthony Whetton,Alan K. Burnett,* Richard L. Darley,*1 and Alex Tonks*1

*Department of Haematology, Institute of Cancer and Genetics, School of Medicine, Cardiff University, Cardiff, UK
†Cardiff Cancer Genomics Biomedical Research Unit, School of Medicine, Cardiff University, Cardiff, UK
‡Faculty of Medical and Human Sciences, Faculty Institute of Cancer Sciences, University of Manchester, Manchester, UK

Acute myeloid leukemia (AML) is characterized by developmental arrest, which is thought to arise from transcriptional dysregulation of myeloid development programs. Hematopoietic stem and progenitor cells (HSPCs) isolated from human blood are frequently used as a normal comparator in AML studies. Previous studies have reported changes in the transcriptional program of genes involved in proliferation, differentiation, apoptosis, and homing when HSPCs were expanded ex vivo. The intrinsic functional differences between quiescent and dividing CD34+
HSPCs prompted us to determine whether fresh or cytokine-induced cord blood-derived CD34+ HSPCs are a more appropriate normal control compared to AML blasts. Based on principal component analysis and gene expression profiling we demonstrate that CD34+ HSPCs that do not undergo ex vivo expansion are transcriptionally similar to minimally differentiated AML blasts. This was confirmed by comparing the cell cycle status of the AML blasts and the HSPCs. We suggest that freshly isolated CD34+ HSPCs that do not undergo ex vivo expansion would serve as a better control to identify novel transcriptional targets in the AML blast population.

Key words: Acute myeloid leukemia (AML); Hematopoietic stem cells; Cell cycle; Gene expression profiling

1These authors provided equal contribution to this work.
Address correspondence to Dr. Alex Tonks, Department of Haematology, Institute of Cancer and Genetics (7th floor), School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK. Tel: (+44) 02920 742235; Fax: (+44) 02920 744655; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Gene Expression, Vol. 16, pp. 177–185, 2015
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DOI: http://dx.doi.org/10.3727/105221615X14399878166195
E-ISSN 1555-3884
Copyright ©
2015 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

Association of Genetic Variants of SIRT1 With Type 2 Diabetes Mellitus

Junfeng Han,*1 Meilin Wei,*1 Qianqian Wang,* Xu Li,* Chaoyu Zhu,* Yueqin Mao,* Li Wei,* Yongning Sun,† and Weiping Jia*

*Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Clinical Center for Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Key Clinical Center for Metabolic Disease, Shanghai, China
†Department of Traditional Chinese Medicine, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China

SIRT1 has been demonstrated in nutrient-sensing and insulin-signaling pathways in in vivo and in vitro experiments, but there is minimal information concerning the association between gene polymorphisms of SIRT1 and type 2 diabetes mellitus (T2DM) in a Chinese Han population. Using case-control design, we recruited 310 unrelated T2DM patients from inpatients at Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, while 301 healthy controls were volunteers from the community for regular medical checkup. All participants were genotyped within the SIRT1 region. The following five SNPs rs10509291, rs12778366, rs10997870, rs10823112, and rs4746720 cover 100% of common genetic variations (minor allele frequency ≥0.05) within theSIRT1 gene (r2 ≥ 0.8). The genotypes of SIRT1 gene polymorphisms were analyzed by the Snapshot assay and DNA sequencing. The resulting data show that there was significant genetic differentiation in rs10823112 [p = 0.003; OR (95% CI) = 1.515 (1.152–1.994) for genotype], rs4746720 [p = 0.024; OR (95% CI) = 1.37 (1.037–1.674) for genotype], and rs10509291 [p = 0.002; OR (95% CI) = 1.551 (1.179–2.04) for genotype] between T2DM and control subjects. However, the result of rs4746720 was no longer significant after correction for multiple testing (p after Bonferroni correction = 0.12); the results of rs10509291and rs10823112 were still significantly different between the two groups (p after Bonferroni correction = 0.01 and 0.015, respectively). Linear regression analyses adjusting for age, gender, and body mass index (BMI) showed that HbA1c and HOMA-IR in subjects with rs10509291 AA genotype were higher than those with TT genotype in T2DM group (p = 0.045, p = 0.035, respectively). Together, our data show that genetic variation of the SIRT1 gene is related to insulin resistance and increase risk of T2DM in Chinese Han population. The risk allele A at SIRT1 rs10509291 was closely associated with T2DM, and subjects who were homozygous of the A allele were more likely to develop T2DM.

Key words: Type 2 diabetes; Genetic variants; SIRT1; Chinese Han population

1These authors provided equal contribution to this work.
Address correspondence to Li Wei, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai Clinical Center for Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Key Clinical Center for Metabolic Disease, 600 Yishan Road, Shanghai 200233, China. Tel: 18930173636; Fax: +8621-64519943; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it  or Yongning Sun, Department of Traditional Chinese Medicine, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, 600 Yishan Road, Shanghai 200233, China. Tel: 18930177579; Fax: +8621-64519943; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Gene Expression, Vol. 16, pp. 187–196, 2015
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DOI: http://dx.doi.org/10.3727/105221615X14399878166230
E-ISSN 1555-3884
Copyright ©
2015 Cognizant Comm. Corp.
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The Histone Acetyltransferase GCN5 Expression Is Elevated and Regulated by c-Myc and E2F1 Transcription Factors in Human Colon Cancer

Yan-Wei Yin,* Hong-Jian Jin,† Wenjing Zhao,* Beixue Gao,‡ Jiangao Fang,‡ Junmin Wei,§ Donna D. Zhang,¶ Jianing Zhang,# and Deyu Fang‡#

*Department of Oncology, Linyi People’s Hospital, and Linyi Tumor Hospital, Linyi, P.R. China
†Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
‡Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
§Department of Chemotherapy, Cancer Center, Qilu Hospital, Shandong University, Jinan, P.R. China
¶Department of Pharmacology and Toxicology, University of Arizona, Tucson, AZ, USA
#School of Life Science and Medicine, Dalian University of Technology, Panjin, P.R. China

The histone acetyltransferase GCN5 has been suggested to be involved in promoting cancer cell growth. But its role in human colon cancer development remains unknown. Herein we discovered that GCN5 expression is significantly upregulated in human colon adenocarcinoma tissues. We further demonstrate that GCN5 is upregulated in human colon cancer at the mRNA level. Surprisingly, two transcription factors, the oncogenic c-Myc and the proapoptotic E2F1, are responsible for GCN5 mRNA transcription. Knockdown of c-Myc inhibited colon cancer cell proliferation largely through downregulating GCN5 transcription, which can be fully rescued by the ectopic GCN5 expression. In contrast, E2F1 expression induced human colon cancer cell death, and suppression of GCN5 expression in cells with E2F1 overexpression further facilitated cell apoptosis, suggesting that GCN5 expression is induced by E2F1 as a possible negative feedback in suppressing E2F1-mediated cell apoptosis. In addition, suppression of GCN5 with its specific inhibitor CPTH2 inhibited human colon cancer cell growth. Our studies reveal that GCN5 plays a positive role in human colon cancer development, and its suppression holds a great therapeutic potential in antitumor therapy.

Key words: E2F1; c-Myc; General control nonrepressed protein 5 (GCN5); Colon cancer; Gene transcription

Address correspondence to Deyu Fang, M.D., Ph.D., Department of Pathology, Northwestern University Feinberg School of Medicine, 303 E. Chicago Avenue, Chicago, IL 60611, USA. Tel: 312-503-3021; Fax: 312-503-3021; Email: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Gene Expression, Vol. 16, pp. 197–203, 2015
1052-2166/13 $90.00
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DOI: http://dx.doi.org/10.3727/105221615X14399878166276
E-ISSN 1555-3884
Copyright ©
2015 Cognizant Comm. Corp.
Printed in the USA. All rights reserved

ELK3 Expression Correlates With Cell Migration, Invasion, and Membrane Type 1-Matrix Metalloproteinase Expression in MDA-MB-231 Breast Cancer Cells

Sun-Hee Heo,*† Je-Yong Lee,*† Kyung-Min Yang,‡ and Kyung-Soon Park*†

*Department of Biomedical Science, College of Life Science, CHA University, Seoul, Korea
†CHA Stem Cell Institute, CHA University, Seoul, Korea
‡CHA Cancer Institute, CHA University, Seoul, Korea

ELK3 is a member of the Ets family of transcription factors. Its expression is associated with angiogenesis, vasculogenesis, and chondrogenesis. ELK3 inhibits endothelial migration and tube formation through the regulation of MT1-MMP transcription. This study assessed the function of ELK3 in breast cancer (BC) cells by comparing its expression between basal and luminal cells in silico and in vitro. In silico analysis showed that ELK3 expression was higher in the more aggressive basal BC cells than in luminal BC cells. Similarly, in vitro analysis showed that ELK3 mRNA and protein expression was higher in basal BC cells than in normal cells and luminal BC cells. To investigate whether ELK3 regulates basal cell migration or invasion, knockdown was achieved by siRNA in the basal BC cell line MDA-MB-231. Inhibition of ELK3 expression decreased cell migration and invasion and downregulated MT1-MMP, the expression of which is positively correlated with tumor cell invasion. In silico analysis revealed that ELK3 expression was associated with that of MT1-MMP in several BC cell lines (0.98 Pearson correlation coefficient). Though MT1-MMP expression was upregulated upon ELK3 nuclear translocation, ELK3 did not directly bind to the 1.3-kb promoter region of the MT1-MMP gene. These results suggest that ELK3 plays a positive role in the metastasis of BC cells by indirectly regulating MT1-MMP expression.

Key words: ELK3; MT1-MMP; Breast cancer; Metastasis

Address correspondence to Kyung-Soon Park, Ph.D., Department of Biomedical Science, College of Life Science and CHA Stem Cell Institute, CHA University, 222 Bundang Gu, Seongnam Si, Kyunggi Do, Korea 463-836. Tel: 82-31-725-8381; Fax: 82-31-725-8350; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it