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Huan He, Indranil Sinha, Rongrong Fan, Lars-Arne Haldosen, Feifei Yan, Chunyan Zhao, Karin Dahlman-Wright
A critical mechanism that has been proposed for transcription regulation by estrogen receptor α (ER) is the tethering of ER to DNA via other transcription factors, such as AP-1. However, genome-wide assessment of the overlap in chromatin binding repertoires of these two transcription factors has not been reported. Here, we show that the AP-1 transcription factor c-Jun interacts with ER and that c-Jun chromatin binding shows extensive overlap with ER binding at the global level. Further, we show that c-Jun overexpression reprograms ER chromatin binding and modulates ER-mediated gene regulation...
February 22, 2018: Oncogene
Ying-Chun Song, Gai-Xia Lu, Hong-Wei Zhang, Xiao-Ming Zhong, Xian-Ling Cong, Shao-Bo Xue, Rui Kong, Dan Li, Zheng-Yan Chang, Xiao-Feng Wang, Yun-Jie Zhang, Ran Sun, Li Chai, Ru-Ting Xie, Ming-Xiang Cai, Ming Sun, Wei-Qing Mao, Hui-Qiong Yang, Yun-Chao Shao, Su-Yun Fan, Ting-Miao Wu, Qing Xia, Zhong-Wei Lv, David A Fu, Yu-Shui Ma
Glioblastoma multiforme (GBM), the most aggressive and lethal primary brain tumor, is characterized by very low life expectancy. Understanding the genomic and proteogenomic characteristics of GBM is essential for devising better therapeutic approaches.Here, we performed proteomic profiling of 8 GBM and paired normal brain tissues. In parallel, comprehensive integrative genomic analysis of GBM was performed in silico using mRNA microarray and sequencing data. Two whole transcript expression profiling cohorts were used - a set of 3 normal brain tissues and 22 glioma tissue samples and a cohort of 5 normal brain tissues and 49 glioma tissue samples...
November 14, 2017: Oncotarget
Yukako Taketani, Kohdai Kitamoto, Toshihiro Sakisaka, Mikiko Kimakura, Tetsuya Toyono, Satoru Yamagami, Shiro Amano, Masahiko Kuroda, Tara Moore, Tomohiko Usui, Yasuo Ouchi
Granular corneal dystrophy (GCD) is an autosomal dominant hereditary disease in which multiple discrete and irregularly shaped granular opacities are deposited in the corneal stroma. GCD is caused by a point mutation in the transforming growth factor-β-induced (TGFBI) gene, located on chromosome 5q31. Here, we report the first successful application of CRISPR-Cas9-mediated genome editing for the correction of a TGFBI mutation in GCD patient-derived primary corneal keratocytes via homology-directed repair (HDR)...
December 1, 2017: Scientific Reports
C Chao-Shern, R Me, L A DeDionisio, B L Ke, M A Nesbit, J Marshall, C B T Moore
PurposeThe post-LASIK exacerbation of corneal dystrophy, otherwise asymptomatic, is almost exclusively associated with the TGFBI gene mutations at codon 124 in exon 4 and codon 555 in exon 12. It is our intention to demonstrate that the pre-operative genetic screening for TGFBI mutations should be mandatory for refractive surgery candidates.Patients and MethodsIn this study, we reviewed the proband's post-LASIK slit-lamp and in vivo confocal microscopy images and genetic testing results, and performed genetic testing on eleven additional members of the family to investigate the penetrance of corneal dystrophy in asymptomatic members who carry the mutation...
January 2018: Eye
Tianhong Pan, Song-Chang Lin, Kai-Jie Yu, Guoyu Yu, Jian H Song, Valerae O Lewis, Justin E Bird, Bryan Moon, Patrick P Lin, Nizar M Tannir, Eric Jonasch, Christopher G Wood, Gary E Gallick, Li-Yuan Yu-Lee, Sue-Hwa Lin, Robert L Satcher
BACKGROUND: Bone metastasis is common in renal cell carcinoma (RCC), and the lesions are mainly osteolytic. The mechanism of bone destruction in RCC bone metastasis is unknown. METHODS: We used a direct intrafemur injection of mice with bone-derived 786-O RCC cells (Bo-786) as an in vivo model to study if inhibition of osteoblast differentiation is involved in osteolytic bone lesions in RCC bone metastasis. RESULTS: We showed that bone-derived Bo-786 cells induced osteolytic bone lesions in the femur of mice...
January 2018: Neoplasia: An International Journal for Oncology Research
Kathleen A Christie, David G Courtney, Larry A DeDionisio, Connie Chao Shern, Shyamasree De Majumdar, Laura C Mairs, M Andrew Nesbit, C B Tara Moore
CRISPR/Cas9 holds immense potential to treat a range of genetic disorders. Allele-specific gene disruption induced by non-homologous end-joining (NHEJ) DNA repair offers a potential treatment option for autosomal dominant disease. Here, we successfully delivered a plasmid encoding S. pyogenes Cas9 and sgRNA to the corneal epithelium by intrastromal injection and acheived long-term knockdown of a corneal epithelial reporter gene, demonstrating gene disruption via NHEJ in vivo. In addition, we used TGFBI corneal dystrophies as a model of autosomal dominant disease to assess the use of CRISPR/Cas9 in two allele-specific systems, comparing cleavage using a SNP-derived PAM to a guide specific approach...
November 23, 2017: Scientific Reports
Ebbe Toftgaard Poulsen, Kasper Runager, Nadia Sukusu Nielsen, Marie V Lukassen, Karen Thomsen, Paige Snider, Olga Simmons, Henrik Vorum, Simon J Conway, Jan J Enghild
TGFBIp is a constituent of the extracellular matrix in many human tissues including the cornea, where it is one of the most abundant proteins expressed. TGFBIp interacts with Type I, II, IV, VI, and XII collagens as well as several members of the integrin family, suggesting it plays an important role in maintaining structural integrity and possibly corneal transparency as well. Significantly, more than 60 point mutations within the TGFBI gene have been reported to result in aberrant TGFBIp folding and aggregation in the cornea, resulting in severe visual impairment and blindness...
January 2018: FEBS Journal
Tao Guan, Lingjie Zhang, Dejian Xu, Haijian Wu, Libin Zheng
OBJECTIVE: To analyze the clinical features and TGFBI gene mutation in a Chinese family affected with Reis-Bucklers corneal dystrophy. METHODS: Genomic DNA was extracted from 53 members including 9 patients from the family. The 17 exons and splice region of introns of the TGFBI gene were amplified by PCR and directly sequenced. All family members were subjected to ophthalmologic examination. RESULTS: A heterozygous mutation (R124L) was found in exon 4 of the TGFBI gene among all patients from the family...
October 10, 2017: Zhonghua Yi Xue Yi Chuan Xue za Zhi, Zhonghua Yixue Yichuanxue Zazhi, Chinese Journal of Medical Genetics
Donghao Shang, Shaozhong Xian, Tiandong Han, Xuanhao Li, Yuting Liu
PURPOSE: To analyse the role of von Hippel-Lindau (VHL) and transforming growth factor β-induced (TGFBI) in synergistic mechanisms of 5-aza-2'-deoxycytidine (DAC) and paclitaxel (PTX) against renal cell carcinoma (RCC). METHODS: To elucidate the role in the synergy between DAC and PTX against RCC cells, TGFBI expression was regulated using siRNA technology and an expression vector containing the full-length cDNA for TGFBI was also transfected into RCC cells. The proliferation of RCC cells was evaluated using the WST-1 assay and TGFBI expression was detected by real-time PCR (RT-PCR), and Western blot...
July 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
Donghao Shang, Bo Song, Yuting Liu
Transforming growth factor-β-induced (TGFΒI) is considered to be a vital gene in several carcinomas. In this study we determined the effect of TGFBI on the proliferative and metastatic potential of human urothelial carcinoma (UC) cells as well as its mRNA and protein expression, which were detected by RT-PCR and Western blot, respectively. UC cell proliferation was analyzed by WST-1 assay and Hoechst 33258 staining. The effect of TGFBI on UC cell metastasis was analyzed using adhesion, migration, and invasion assays...
September 22, 2017: Cancer Science
Wei-Yu Chen, Yuan-Chin Tsai, Hsiu-Lien Yeh, Florent Suau, Kuo-Ching Jiang, Ai-Ning Shao, Jiaoti Huang, Yen-Nien Liu
Androgen deprivation therapy (ADT) targeting the androgen receptor (AR) is a standard therapeutic regimen for treating prostate cancer. However, most tumors progress to metastatic castration-resistant prostate cancer after ADT. We identified the type 1, 2, and 4 collagen-binding protein transforming growth factor-β (TGFβ)-induced protein (TGFBI) as an important factor in the epithelial-to-mesenchymal transition (EMT) and malignant progression of prostate cancer. In prostate cancer cell lines, AR signaling stimulated the activity of the transcription factor SPDEF, which repressed the expression of TGFBI ADT, AR antagonism, or overexpression of TGFBI inhibited the activity of SPDEF and enhanced the proliferation rates of prostate cancer cells...
August 15, 2017: Science Signaling
Jonas D Van Belleghem, Frédéric Clement, Maya Merabishvili, Rob Lavigne, Mario Vaneechoutte
The ability of bacteriophages to kill bacteria is well known, as is their potential use as alternatives to antibiotics. As such, bacteriophages reach high doses locally through infection of their bacterial host in the human body. In this study we assessed the gene expression profile of peripheral blood monocytes from six donors for twelve immunity-related genes (i.e. CD14, CXCL1, CXCL5, IL1A, IL1B, IL1RN, IL6, IL10, LYZ, SOCS3, TGFBI and TNFA) induced by Staphylococcus aureus phage ISP and four Pseudomonas aeruginosa phages (i...
August 14, 2017: Scientific Reports
Jennifer A Schwanekamp, Angela Lorts, Michelle A Sargent, Allen J York, Kelly M Grimes, Demetria M Fischesser, Jason J Gokey, Jeffrey A Whitsett, Simon J Conway, Jeffery D Molkentin
Extracellular matrix production and accumulation stabilize the heart under normal conditions as well as form a protective scar after myocardial infarction injury, although excessive extracellular matrix accumulation with long-standing heart disease is pathological. In the current study we investigate the role of the matricellular protein, transforming growth factor beta-induced (TGFBI), which is induced in various forms of heart disease. Additionally, we sought to understand whether TGFBI is functionally redundant to its closely related family member periostin, which is also induced in the diseased heart...
2017: PloS One
Anandalakshmi Venkatraman, Bamaprasad Dutta, Elavazhagan Murugan, Hao Piliang, Rajamani Lakshminaryanan, Anita Chan Sook Yee, Konstantin V Pervushin, Siu Kwan Sze, Jodhbir S Mehta
TGFBI-associated corneal dystrophies are inherited disorders caused by TGFBI gene variants that promote deposition of mutant protein (TGFBIp) as insoluble aggregates in the cornea. Depending on the type and position of amino acid substitution, the aggregates may be amyloid fibrillar, amorphous globular or both, but the molecular mechanisms that drive these different patterns of aggregation are not fully understood. In the current study, we report the protein composition of amyloid corneal aggregates from lattice corneal dystrophy patients of Asian origin with H626R and R124C mutation and compared it with healthy corneal tissues via LC-MS/MS...
July 20, 2017: Journal of Proteome Research
Radosław Januchowski, Karolina Sterzyńska, Piotr Zawierucha, Marcin Ruciński, Monika Świerczewska, Małgorzata Partyka, Katarzyna Bednarek-Rajewska, Maciej Brązert, Michał Nowicki, Maciej Zabel, Andrzej Klejewski
PURPOSE: The present study is to discover a new genes associated with drug resistance development in ovarian cancer. METHODS: We used microarray analysis to determine alterations in the level of expression of genes in cisplatin- (CisPt), doxorubicin- (Dox), topotecan- (Top), and paclitaxel- (Pac) resistant variants of W1 and A2780 ovarian cancer cell lines. Immunohistochemistry assay was used to determine protein expression in ovarian cancer patients. RESULTS: We observed alterations in the expression of 22 genes that were common to all three cell lines that were resistant to the same cytostatic drug...
July 25, 2017: Oncotarget
Xianli Du, Peng Chen, Dapeng Sun
PURPOSE: This study is to summarize the concurrent keratoconus (KC) and granular corneal dystrophy (GCD) phenotype and identify the underlying genetic cause in a 23-year-old male patient. METHODS: A detailed family history and clinical data from the patient and his parents were collected by ophthalmologic examination. The candidate genes were captured and sequenced by targeted next-generation sequencing, and the results were confirmed by Sanger sequencing. RESULTS: The proband was clinically diagnosed as a case of concurrent KC and GCD, which is a very rare presentation...
May 31, 2017: Graefe's Archive for Clinical and Experimental Ophthalmology
Donghao Shang, Shaozhong Xian, Tiandong Han, Xuanhao Li, Yuting Liu
PURPOSE: To analyse the role of von Hippel-Lindau (VHL) and transforming growth factor β-induced (TGFBI) in synergistic mechanisms of 5-aza-2'-deoxycytidine (DAC) and paclitaxel (PTX) against renal cell carcinoma (RCC). METHODS: To elucidate the role in the synergy between DAC and PTX against RCC cells, TGFBI expression was regulated using siRNA technology and an expression vector containing the full-length cDNA for TGFBI was also transfected into RCC cells. The proliferation of RCC cells was evaluated using the WST-1 assay and TGFBI expression was detected by real-time PCR (RT-PCR), and Western blot...
March 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
Liang Zhang, Yi Huang, Wenlei Zhuo, Yi Zhu, Bo Zhu, Zhengtang Chen
Lapatinib, a novel oral dual tyrosine kinase inhibitor blocking HER1 and HER2 pathways, has presented beneficial effects on breast cancer with positive HER2. However, its efficacy is largely limited by the occurrence of acquired drug resistance. In this study, we aimed to explore the underlying molecular mechanisms of Lapatinib resistance using bioinformatics strategies. The gene expression profile of SKBR3-R (acquired Lapatinib-resistant) and SKBR3 (Lapatinib-sensitive) cell line was downloaded from gene expression omnibus database...
May 2017: Medical Oncology
Wen-Ping Cao, Hai-Gang Yuan, Ping Liu, Xue Li, Qi Hu
AIM: To report a phenotypic variant pedigree of lattice corneal dystrophy (LCD) associated with two mutations, R124C and A546D, in the transforming growth factor beta-induced gene (TGFBI). METHODS: A detailed ocular examination was taken for all participants of a LCD family. Peripheral blood leukocytes from each participant were extracted to obtain the DNA. Polymerase chain reaction (PCR) of all seventeen exons of TGFBI gene was performed. The products were sequenced and analyzed...
2017: International Journal of Ophthalmology
Venkatraman Anandalakshmi, Elavazhagan Murugan, Eunice Goh Tze Leng, Lim Wei Ting, Shyam S Chaurasia, Toshio Yamazaki, Toshio Nagashima, Benjamin Lawrence George, Gary Swee Lim Peh, Konstantin Pervushin, Rajamani Lakshminarayanan, Jodhbir S Mehta
Corneal stromal dystrophies are a group of genetic disorders that may be caused by mutations in the transforming growth factor β-induced (TGFBI) gene which results in the aggregation and deposition of mutant proteins in various layers of the cornea. The type of amino acid substitution dictates the age of onset, anatomical location of the deposits, morphological features of deposits (amyloid, amorphous powder or a mixture of both forms) and the severity of disease presentation. It has been suggested that abnormal turnover and aberrant proteolytic processing of the mutant proteins result in the accumulation of insoluble protein deposits...
May 9, 2017: Biochemical Journal
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