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Jia Nan, Wang Jieyu, Li Qing, Tao Xiang, Chang Kaikai, Hua Keqin, Yu Yinhua, Wong Kwong-Kwok, Feng Weiwei
This work investigated the role of paired box 2 (PAX2) in endometrial cancer and its epigenetic regulation mechanism. Endometrial cancer tissues and cell lines exhibited increased PAX2 expression compared with hyperplasia, normal endometrium and endometrial epithelial cells. Knock-down of PAX2 resulted in reduced cell viability, invasion and migration, and PAX2 overexpression caused the opposite effects. Increased methylation of the PAX2 promoter was observed in both cancer tissues and cell lines and was positively correlated with PAX2 expression...
October 13, 2016: Oncotarget
Saurabh Priyadarshi, Kirtal Hansdah, Chinmay Sundar Ray, Narayan Chandra Biswal, Puppala Venkat Ramchander
Otosclerosis (OTSC) is defined by abnormal bone remodeling in the otic capsule of middle ear which leads to conductive hearing loss. In our previous study, we have identified a de novo heterozygous mutation -832G > A in the promoter of TGFB1 in an otosclerosis patient. In the present study, we progressively screened this mutation in a cohort of 254 cases and 262 controls. The family members of the patient positive for -832G > A variation were also screened and found inheritance of this variation only to her daughter...
2016: Scientific Reports
Liduan Zheng, Wanju Jiao, Hong Mei, Huajie Song, Dan Li, Xuan Xiang, Yajun Chen, Feng Yang, Huanhuan Li, Kai Huang, Qiangsong Tong
Matrix metalloproteinase 14 (MMP-14), a membrane-anchored MMP that promotes the tumorigenesis and aggressiveness, is highly expressed in gastric cancer. However, the transcriptional regulators of MMP-14 expression in gastric cancer still remain largely unknown. In this study, through mining computational algorithm programs and chromatin immunoprecipitation datasets, we identified adjacent binding sites of myeloid zinc finger 1 (MZF1) and miRNA-337-3p (miR-337-3p) within the MMP-14 promoter. We demonstrated that MZF1 directly bound to the MMP-14 promoter to facilitate its nascent transcription and expression in gastric cancer cell lines...
May 31, 2016: Oncotarget
Gareth J McKay, David H Kavanagh, John K Crean, Alexander P Maxwell
OBJECTIVE: WNT/β-catenin pathway members have been implicated in interstitial fibrosis and glomerular sclerosis disease processes characteristic of diabetic nephropathy (DN), processes partly controlled by transcription factors (TFs) that bind to gene promoter regions attenuating regulation. We sought to identify predicted cis-acting transcription factor binding sites (TFBSs) overrepresented within WNT pathway members. METHODS: We assessed 62 TFBS motif frequencies from the JASPAR databases in 65 WNT pathway genes...
2016: Journal of Diabetes Research
Jinqiu Zhu, Amber Dubois, Yichen Ge, James A Olson, Xuefeng Ren
INTRODUCTION: High-throughput loss-of-function genetic screening tools in yeast or other model systems except in mammalian cells have been implemented to study human susceptibility to chemical toxicity. Here, we employed a newly developed human haploid cell (KBM7)-based mutagenic screening model (KBM7-mu cells) and examined its applicability in identifying genes whose absence allows cells to survive and proliferate in the presence of chemicals. METHODS: KBM7-mu cells were exposed to 200 μM Chlorpyrifos (CPF), a widely used organophosphate pesticide, a dose causing approximately 50% death of cells after 48h of treatment...
November 2015: Journal of Pharmacological and Toxicological Methods
Erming Tian, Magne Børset, Jeffrey R Sawyer, Gaute Brede, Thea K Våtsveen, Håkon Hov, Anders Waage, Bart Barlogie, John D Shaughnessy, Joshua Epstein, Anders Sundan
The growth and survival factor hepatocyte growth factor (HGF) is expressed at high levels in multiple myeloma (MM) cells. We report here that elevated HGF transcription in MM was traced to DNA mutations in the promoter alleles of HGF. Sequence analysis revealed a previously undiscovered single-nucleotide polymorphism (SNP) and crucial single-nucleotide variants (SNVs) in the promoters of myeloma cells that produce large amounts of HGF. The allele-specific mutations functionally reassembled wild-type sequences into the motifs that affiliate with endogenous transcription factors NFKB (nuclear factor kappa-B), MZF1 (myeloid zinc finger 1), and NRF-2 (nuclear factor erythroid 2-related factor 2)...
November 2015: Genes, Chromosomes & Cancer
Carmen S Metzger, Dimitrios Koutsimpelas, Juergen Brieger
Overexpression of the vascular endothelial growth factor (VEGF) gene has been associated with advanced stage and poor survival in several cancers. The majority of disease-associated VEGF-single nucleotide polymorphisms (SNPs) locate within regulatory regions. Therefore, an influence of SNPs located in the promoter/5'-untranslated region (5'UTR) on transcription factor binding (TFB) and gene expression seems feasible. We reviewed the literature investigating a potential connection of VEGF-SNPs and transcriptional regulation of the VEGF gene...
December 2015: Cytokine
Taka Eguchi, Thomas Prince, Barbara Wegiel, Stuart K Calderwood
Myeloid zinc finger 1 (MZF1) belongs to the SCAN-Zinc Finger (SCAN-ZF) transcription factor family that has recently been implicated in a number of types of cancer. Although the initial studies concentrated on the role of MZF1 in myeloid differentiation and leukemia, the factor now appears to be involved in the etiology of major solid tumors such as lung, cervical, breast, and colorectal cancer. Here we discuss the regulation of MZF1 that mediated its recruitment and activation in cancer, concentrating on posttranslational modification by phosphorylation, and sumoylation, formation of promyelocytic leukemia nuclear bodies and its association with co-activators and co-repressors...
October 2015: Journal of Cellular Biochemistry
Richard T Piszczatowski, Brian J Rafferty, Andre Rozado, James V Parziale, Nathan H Lents
Connective Tissue Growth Factor (CCN2/CTGF) and Nephroblastoma Overexpressed (CCN3/NOV) execute key functions within the hematopoietic compartment. Both are abundant in the bone marrow stroma, which is a niche for hematopoiesis and supports marrow function. Roles for 1,25-dihydroxyvitamin D3 (calcitriol) and all-trans retinoic acid in the bone marrow have also been elucidated. Interestingly, some of the annotated roles of these vitamins overlap with established functions of CCN2 and CCN3. Yet, no factor has been identified that unifies these observations...
November 2015: Journal of Cellular Physiology
Deeksha Vishwamitra, Choladda V Curry, Serhan Alkan, Yao-Hua Song, Gary E Gallick, Ahmed O Kaseb, Ping Shi, Hesham M Amin
BACKGROUND: The type I insulin-like growth factor receptor (IGF-IR) tyrosine kinase promotes the survival of an aggressive subtype of T-cell lymphoma by interacting with nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) oncogenic protein. NPM-ALK(+) T-cell lymphoma exhibits much higher levels of IGF-IR than normal human T lymphocytes. The mechanisms underlying increased expression of IGF-IR in this lymphoma are not known. We hypothesized that upregulation of IGF-IR could be attributed to previously unrecognized defects that inherently exist in the transcriptional machinery in NPM-ALK(+) T-cell lymphoma...
2015: Molecular Cancer
Chung-Po Ko, Li-Chiu Yang, Chih-Jung Chen, Kun-Tu Yeh, Shu-Hui Lin, Shun-Fa Yang, Mu-Kuan Chen, Chiao-Wen Lin
The myeloid zinc finger 1 (MZF1) is a zinc finger transcription factor which regulates myeloid differentiation and oncogenesis. However, little information is available concerning the MZF1 expression in oral squamous cell carcinoma (OSCC) and its correlation with patients' prognosis. We detected the expression of MZF1 in 274 patients with OSCC using tissue microarrays (TMAs) and evaluated the associations between nuclear MZF1 expression and the clinical parameters of OSCC patients. We found that nuclear MZF1 expression was present in 190/274 (69...
September 2015: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Xiaoping Liu, Qianqian Lei, Zhibin Yu, Gang Xu, Hailin Tang, Wei Wang, Zeyou Wang, Guiyuan Li, Minghua Wu
LIM-only protein 3 (LMO3), a member of the LIM-only protein group, is a new DNA methylation gene that was identified in gliomas via the MeDIP-Chip in our previous study. In this study, we found that LIM-only protein 3 (LMO3) is hypomethylated and overexpressed in glioma cells and tissues. The overexpression of LMO3 was correlated with a poor prognosis in glioma patients, and LMO3 was indirectly inhibited by the tumor suppressor miR-101, which is a potential prognosis marker of gliomas. MiR-101 decreased the expression of LMO3 by reversing the methylation status of the LMO3 promoter and by inhibiting the presence of the methylation-related histones H3K4me2 and H3K27me3 and increasing the presence of H3K9me3 and H4K20me3 on the promoter...
April 10, 2015: Oncotarget
Joseph Driver, Cynthia E Weber, John J Callaci, Anai N Kothari, Matthew A Zapf, Philip M Roper, Dariusz Borys, Carrie A Franzen, Gopal N Gupta, Philip Y Wai, Jiwang Zhang, Mitchell F Denning, Paul C Kuo, Zhiyong Mi
Alcohol (EtOH) intoxication is a risk factor for increased morbidity and mortality with traumatic injuries, in part through inhibition of bone fracture healing. Animal models have shown that EtOH decreases fracture callus volume, diameter, and biomechanical strength. Transforming growth factor β1 (TGF-β1) and osteopontin (OPN) play important roles in bone remodeling and fracture healing. Mesenchymal stem cells (MSC) reside in bone and are recruited to fracture sites for the healing process. Resident MSC are critical for fracture healing and function as a source of TGF-β1 induced by local OPN, which acts through the transcription factor myeloid zinc finger 1 (MZF1)...
April 17, 2015: Journal of Biological Chemistry
Zhisong Li, Xiyao Gu, Linlin Sun, Shaogen Wu, Lingli Liang, Jing Cao, Brianna Marie Lutz, Alex Bekker, Wei Zhang, Yuan-Xiang Tao
Peripheral nerve injury-induced changes in gene transcription and translation in primary sensory neurons of the dorsal root ganglion (DRG) are considered to contribute to neuropathic pain genesis. Transcription factors control gene expression. Peripheral nerve injury increases the expression of myeloid zinc finger protein 1 (MZF1), a transcription factor, and promotes its binding to the voltage-gated potassium 1.2 (Kv1.2) antisense (AS) RNA gene in the injured DRG. However, whether DRG MZF1 participates in neuropathic pain is still unknown...
April 2015: Pain
Guoting Chen, Hengping Li, Xianping Niu, Guofeng Li, Ning Han, Xin Li, Guang Li, Yangzhou Liu, Guixin Sun, Yong Wang, Zengchun Li, Qinchuan Li
Colorectal cancer (CRC) is among the most lethal human cancers, but the mechanism of the cancer is still unclear enough. We aimed to explore the key genes in CRC progression. The gene expression profile (GSE4183) of CRC was obtained from Gene Expression Omnibus database which included 8 normal samples, 15 adenoma samples, 15 CRC samples and 15 inflammatory bowel disease (IBD) samples. Thereinto, 8 normal, 15 adenoma, and 15 CRC samples were chosen for our research. The differentially expressed genes (DEGs) in normal vs...
July 2015: Pathology Oncology Research: POR
C E Weber, A N Kothari, P Y Wai, N Y Li, J Driver, M A C Zapf, C A Franzen, G N Gupta, C Osipo, A Zlobin, W K Syn, J Zhang, P C Kuo, Z Mi
Interactions between tumor cells and cancer-associated fibroblasts (CAFs) in the tumor microenvironment significantly influence cancer growth and metastasis. Transforming growth factor-β (TGF-β) is known to be a critical mediator of the CAF phenotype, and osteopontin (OPN) expression in tumors is associated with more aggressive phenotypes and poor patient outcomes. The potential link between these two pathways has not been previously addressed. Utilizing in vitro studies using human mesenchymal stem cells (MSCs) and MDA-MB231 (OPN+) and MCF7 (OPN-) human breast cancer cell lines, we demonstrate that OPN induces integrin-dependent MSC expression of TGF-β1 to mediate adoption of the CAF phenotype...
September 10, 2015: Oncogene
Stefanie A Doppler, Astrid Werner, Melanie Barz, Harald Lahm, Marcus-André Deutsch, Martina Dreßen, Matthias Schiemann, Bernhard Voss, Serge Gregoire, Rajarajan Kuppusamy, Sean M Wu, Rüdiger Lange, Markus Krane
Vertebrate heart development is strictly regulated by temporal and spatial expression of growth and transcription factors (TFs). We analyzed nine TFs, selected by in silico analysis of an Nkx2.5 enhancer, for their ability to transactivate the respective enhancer element that drives, specifically, expression of genes in cardiac progenitor cells (CPCs). Mzf1 showed significant activity in reporter assays and bound directly to the Nkx2.5 cardiac enhancer (Nkx2.5 CE) during murine ES cell differentiation. While Mzf1 is established as a hematopoietic TF, its ability to regulate cardiogenesis is completely unknown...
2014: PloS One
Po-Ming Chen, Ya-Wen Cheng, Yao-Chen Wang, Tzu-Chin Wu, Chih-Yi Chen, Huei Lee
PURPOSE: Foxhead box M1 (FOXM1) expression has been shown to be linked with human papillomavirus (HPV) 16/18-infected cervical cancer. However, the mechanism underlying the induction of FOXM1 in HPV 16/18-infected cancers remains elusive. EXPERIMENTAL DESIGN: The mechanistic actions of FOXM1 induced by the E6/NKX2-1 axis in tumor aggressiveness were elucidated in cellular and animal models. The prognostic value of FOXM1 for overall survival (OS) and relapse-free survival (RFS) in HPV-positive oral and lung cancers was assessed using Kaplan-Meier and Cox regression models...
November 2014: Neoplasia: An International Journal for Oncology Research
X D Kong, N Liu, X J Xu
In this study, biomarkers and transcriptional factor motifs were identified in order to investigate the etiology and phenotypic severity of Down syndrome. GSE 1281, GSE 1611, and GSE 5390 were downloaded from the gene expression ominibus (GEO). A robust multiarray analysis (RMA) algorithm was applied to detect differentially expressed genes (DEGs). In order to screen for biological pathways and to interrogate the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database, the database for annotation, visualization, and integrated discovery (DAVID) was used to carry out a gene ontology (GO) function enrichment for DEGs...
October 2014: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
Mano Horinaka, Tatsushi Yoshida, Mitsuhiro Tomosugi, Shusuke Yasuda, Yoshihiro Sowa, Toshiyuki Sakai
A combined therapy of sulindac sulfide and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising strategy for the treatment of cancer. Sulindac sulfide had been shown to induce the expression of death receptor 5 (DR5), a receptor for TRAIL, and sensitize cancer cells to TRAIL-induced apoptosis; however, the molecular mechanism underlying the upregulation of DR5 has not yet been elucidated. We demonstrate here that myeloid zinc finger 1 (MZF1) mediates the induction of DR5 by sulindac sulfide...
2014: Scientific Reports
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