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Cheng-En Hu, Jun Gan
There is substantial research on the oncogenic role of tripartite motif containing 37 (TRIM37); however, its importance in colorectal cancer (CRC) remains to be elucidated. The present study used reverse transcription‑quantitative polymerase chain reaction, immunohistochemistry and western blotting to detect the expression level of TRIM37 in CRC. The importance of TRIM37 in cell proliferation, invasion and metastasis of CRC were investigated through overexpressing or knocking‑down of TRIM37 in CRC cell lines, to observe its function...
January 16, 2017: Molecular Medicine Reports
Jogender Tushir-Singh, Sanchita Bhatnagar
In mammals, gene expression is largely controlled at the transcriptional level. In response to environmental or intrinsic signaling, gene expression is often fine-tuned by epigenetic modifications, including DNA methylation and histone modifications. One such histone modification is ubiquitination that predominately occurs in mono-ubiquitinated forms on histone H2A and H2B. We recently identified and characterized a novel E3 ligase called TRIM37 that ubiquitinates H2A. This study highlights the consequence of aberrant histone ubiquitination at the promoters of tumor suppressor genes in breast cancer...
2017: Methods in Molecular Biology
Franz Meitinger, John V Anzola, Manuel Kaulich, Amelia Richardson, Joshua D Stender, Christopher Benner, Christopher K Glass, Steven F Dowdy, Arshad Desai, Andrew K Shiau, Karen Oegema
In normal human cells, centrosome loss induced by centrinone-a specific centrosome duplication inhibitor-leads to irreversible, p53-dependent G1 arrest by an unknown mechanism. A genome-wide CRISPR/Cas9 screen for centrinone resistance identified genes encoding the p53-binding protein 53BP1, the deubiquitinase USP28, and the ubiquitin ligase TRIM37. Deletion of TP53BP1, USP28, or TRIM37 prevented p53 elevation in response to centrosome loss but did not affect cytokinesis failure-induced arrest or p53 elevation after doxorubicin-induced DNA damage...
July 18, 2016: Journal of Cell Biology
Kaisa M Kettunen, Riitta Karikoski, Riikka H Hämäläinen, Teija T Toivonen, Vasily D Antonenkov, Natalia Kulesskaya, Vootele Voikar, Maarit Hölttä-Vuori, Elina Ikonen, Kirsi Sainio, Anu Jalanko, Susann Karlberg, Niklas Karlberg, Marita Lipsanen-Nyman, Jorma Toppari, Matti Jauhiainen, J Kalervo Hiltunen, Hannu Jalanko, Anna-Elina Lehesjoki
Mulibrey nanism (MUL) is a rare autosomal recessive multi-organ disorder characterized by severe prenatal-onset growth failure, infertility, cardiopathy, risk for tumors, fatty liver, and type 2 diabetes. MUL is caused by loss-of-function mutations in TRIM37, which encodes an E3 ubiquitin ligase belonging to the tripartite motif (TRIM) protein family and having both peroxisomal and nuclear localization. We describe a congenic Trim37 knock-out mouse (Trim37(-/-)) model for MUL. Trim37(-/-) mice were viable and had normal weight development until approximately 12 months of age, after which they started to manifest increasing problems in wellbeing and weight loss...
2016: Biology Open
Jianxin Jiang, She Tian, Chao Yu, Meiyuan Chen, Chengyi Sun
Increasing evidence indicated that tripartite motif containing 37 (TRIM37) was involved in the tumorigenesis of several cancer types. However, its expression pattern and biological functions in pancreatic ductal adenocarcinoma (PDAC) remained unknown. In this study, real-time PCR, Western blot and immunohistochemistry was performed to examine the expression of TRIM37 in the pancreatic cancerous tissues. Colony formation assay and cell migration assay were performed to study the functions of TRIM37 in pancreatic cancer cells...
February 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Jianxin Jiang, Chao Yu, Meiyuan Chen, She Tian, Chengyi Sun
Hepatocellular carcinoma (HCC) is the most common cancer in the world especially in East Asia and Africa. Advanced stage, metastasis and frequent relapse are responsible for the poor prognosis of HCC. However, the precise mechanisms underlying HCC remained unclear. So it is urgent to identify the pathological processes and relevant molecules of HCC. TRIM37 is an E3 ligase and has been observed deregulated expression in various tumors. Recent studies of TRIM37 have implicated that TRIM37 played critical roles in cell proliferation and other processes...
September 4, 2015: Biochemical and Biophysical Research Communications
Sanchita Bhatnagar, Claude Gazin, Lynn Chamberlain, Jianhong Ou, Xiaochun Zhu, Jogender S Tushir, Ching-Man Virbasius, Ling Lin, Lihua J Zhu, Narendra Wajapeyee, Michael R Green
The TRIM37 (also known as MUL) gene is located in the 17q23 chromosomal region, which is amplified in up to ∼ 40% of breast cancers. TRIM37 contains a RING finger domain, a hallmark of E3 ubiquitin ligases, but its protein substrate(s) is unknown. Here we report that TRIM37 mono-ubiquitinates histone H2A, a chromatin modification associated with transcriptional repression. We find that in human breast cancer cell lines containing amplified 17q23, TRIM37 is upregulated and, reciprocally, the major H2A ubiquitin ligase RNF2 (also known as RING1B) is downregulated...
December 4, 2014: Nature
Marianne Brodtkorb, Ole Christian Lingjærde, Kanutte Huse, Gunhild Trøen, Marit Hystad, Vera I Hilden, June H Myklebust, Ellen Leich, Andreas Rosenwald, Jan Delabie, Harald Holte, Erlend B Smeland
Transformation of follicular lymphoma (FL) to a more aggressive disease is associated with rapid progression and death. Existing molecular markers for transformation are few and their clinical impact is limited. Here, we report on a whole-genome study of DNA copy numbers and gene expression profiles in serial FL biopsies. We identified 698 genes with high correlation between gene expression and copy number, and the molecular network most enriched for these cis-associated genes. This network includes 14 cis-associated genes directly related to the nuclear factor κB (NF-κB) pathway...
February 13, 2014: Blood
Fernando R Balestra, Petr Strnad, Isabelle Flückiger, Pierre Gönczy
Centrioles are essential for forming cilia, flagella, and centrosomes and are thus critical for a range of fundamental cellular processes. Despite their importance, the mechanisms governing centriole biogenesis remain incompletely understood. We performed a high-content genome-wide small-interfering-RNA-based screen to identify genes regulating centriole formation in human cells. We designed an algorithm to automatically detect GFP-Centrin foci that, combined with subsequent manual analysis, allowed us to identify 44 genes required for centriole formation and 32 genes needed for restricting centriole number...
June 24, 2013: Developmental Cell
Matthias Kumpf, Riikka H Hämäläinen, Michael Hofbeck, Winfried Baden
UNLABELLED: Mulibrey nanism (MUL) is a rare autosomal recessive disorder with severe primordial growth retardation and multiorgan involvement, caused by mutations in TRIM37. Early clinical detection is important since more than 50 % of the patients develop congestive heart failure. We report a 12-year-old patient who presented in infancy with severe growth retardation, dysmorphic features, and cleft palate. Clinical diagnosis of MUL was established at the age of 5 years. Postmortem, molecular diagnostic confirmed MUL as a novel 1-bp deletion (c...
October 2013: European Journal of Pediatrics
Seung Woo Shin, Tae Jeong Oh, Se-Min Park, Jong Sook Park, An Soo Jang, Sung Woo Park, Soo Taek Uh, Sungwhan An, Choon-Sik Park
PURPOSE: We sought to identify asthma-related genes and to examine the potential of these genes to predict asthma, based on expression levels. METHODS: The subjects were 42 asthmatics and 10 normal healthy controls. PBMC RNA was subjected to microarray analysis using a 35K array; t-tests were used to identify genes that were expressed differentially between the two groups. A multiple logistic regression analysis was applied to the differentially expressed genes, and area under the curve (AUC) values from receiver operating characteristic (ROC) curves were obtained...
October 2011: Allergy, Asthma & Immunology Research
Susann Karlberg, Jorma Toppari, Niklas Karlberg, Mirja Nurmio, Riitta Karikoski, Hannu Jalanko, Marita Lipsanen-Nyman
CONTEXT: Few monogenic mutations causing human male infertility have been identified to date. OBJECTIVE: We studied pubertal development and fecundity in males with Mulibrey nanism (MUL) caused by mutations in the TRIM37 gene. DESIGN, SETTING, AND PATIENTS: Twenty-eight male MUL patients of the Finnish national cohort aged 8.7 to 50.0 yr (median age, 28.8) at the end of observation were followed for 10 yr beginning from 2000-2001. MAIN OUTCOME MEASURES: Clinical characteristics, reproductive hormone levels, semen quality, and testicular histology were assessed...
November 2011: Journal of Clinical Endocrinology and Metabolism
Musaffe Tuna, Marcel Smid, John W M Martens, John A Foekens
Many studies have examined DNA copy number changes or gene expression profiling and their association with clinical outcomes in breast cancer. However, until now no study has investigated whether acquired uniparental disomy (aUPD), in which both chromosomes in a pair are derived from the same parent, may have an association with clinical outcome including initiation and recurrence of breast cancer. In this study, we used high-density SNP and expression microarrays data from primary tumors of 313 lymph node-negative breast cancer patients who had not received adjuvant systemic therapy to evaluate the association of aUPD with metastasis-free survival (MFS) and overall survival (OS)...
February 2012: Breast Cancer Research and Treatment
Niklas Karlberg, Susann Karlberg, Riitta Karikoski, Sakari Mikkola, Marita Lipsanen-Nyman, Hannu Jalanko
Mulibrey nanism (MUL) is a monogenic disorder with prenatal-onset growth failure, typical clinical characteristics, cardiopathy and tendency for a metabolic syndrome. It is caused by recessive mutations in the TRIM37 gene encoding for the peroxisomal TRIM37 protein with ubiquitin-ligase activity. In this work, the frequency and pathology of malignant and benign tumours were analysed in a national cohort of 89 Finnish MUL patients aged 0.7-76 years. The subjects had a clinical and radiological evaluation, and histological and immunohistocemical analyses on specimens obtained from biopsy, surgery or autopsy, were performed...
June 2009: Journal of Pathology
Susann Karlberg, Marita Lipsanen-Nyman, Heini Lassus, Jukka Kallijärvi, Anna-Elina Lehesjoki, Ralf Butzow
Mulibrey nanism is an autosomal recessive growth disorder caused by mutations in the TRIM37 gene encoding a protein of unknown function. More than half of female patients with Mulibrey nanism develop benign mesenchymal tumors of ovarian sex cord-stromal origin. In this work, we characterize the gynecological tumors of female patients with Mulibrey nanism in detail. In addition to tumors of the fibrothecoma group, 18% (4/22) of the patients were observed with epithelial neoplasias, including 2 ovarian adenofibromas, 1 ovarian poorly differentiated adenocarcinoma and 1 endometrial adenocarcinoma...
April 2009: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Tümay Doğanc, Berrin E Yüksel Konuk, Nursel Alpan, Onur Konuk, Riikka H Hämäläinen, Anna-Elina Lehesjoki, Mustafa Tekin
Mulibrey nanism is a rare autosomal-recessive disorder characterized by prenatal onset severe growth retardation and pericardial constriction associated with abnormalities of muscle, liver, brain and eye. More than 80% of previously reported patients are of Finnish origin in whom a founder mutation in the TRIM37 gene have been described. We report on a 7-year-old Turkish boy who presented with classical phenotypic features of mulibrey nanism. Mutation screening of the TRIM37 gene revealed that the proband had a homozygous two base pair deletion, c...
July 2007: Clinical Dysmorphology
R H Hämäläinen, D Mowat, M T Gabbett, T A O'brien, J Kallijärvi, A-E Lehesjoki
Mulibrey nanism is a rare autosomal recessive growth disorder with prenatal onset, including occasional progressive cardiopathy, characteristic facial features, failure of sexual maturation, insulin resistance with type 2 diabetes, and an increased risk for Wilms' tumor. Mulibrey nanism is prevalent in the Finnish population and appears extremely rare elsewhere. However, cases outside of Finland may be underdiagnosed or misdiagnosed as having the 3-M or Silver-Russell syndrome, two important differential diagnostic disorders...
December 2006: Clinical Genetics
Jukka Kallijärvi, Riikka H Hämäläinen, Niklas Karlberg, Kirsi Sainio, Anna-Elina Lehesjoki
Mutations in the TRIM37 gene underlie mulibrey nanism (muscle-liver-brain-eye nanism), a rare monogenic developmental disorder characterized by severe growth failure, characteristic dysmorphic features, cardiopathy, failure of sexual maturation, and metabolic syndrome. The TRIM37 protein, a member of the tripartite motif subfamily of RING finger proteins, is highly conserved between human and mouse. High evolutionary conservation is seen also at the gene level. We here show that the mouse Trim37 gene presents several alternative splice variants, including a testis-specific transcript with an additional 3' exon...
September 2006: Histochemistry and Cell Biology
Riikka H Hämäläinen, Tarja Joensuu, Jukka Kallijärvi, Anna-Elina Lehesjoki
The TRIM37 gene encodes a peroxisomal protein of unknown function. Mutations in TRIM37 underlie mulibrey nanism, a rare autosomal recessively inherited disorder with severe growth failure of prenatal onset, constrictive pericardium, hepatomegaly and characteristic dysmorphic features. Eleven mulibrey nanism-associated mutations have been identified. We here characterised TRIM37 further by mapping the transcription initiation site and promoter region as well as by analysing splice variants. By primer extension analysis, several transcription initiation sites were localised to a region between -246 and -373 relative to the ATG codon for translation initiation...
January 17, 2006: Gene
Niklas Karlberg, Hannu Jalanko, Jukka Kallijärvi, Anna-Elina Lehesjoki, Marita Lipsanen-Nyman
We evaluated the glucose and lipid metabolism in 65 patients (aged 1.1-55 years) with mulibrey (muscle-liver-brain-eye) nanism (MUL), which is a monogenic disorder with prenatal-onset growth failure and typical clinical characteristics. MUL is caused by mutations in the TRIM37 gene, encoding a peroxisomal protein (TRIM37) with E3 ubiquitin-ligase activity. The subjects underwent clinical evaluation, abdominal ultrasonography, and laboratory measurements, including a 3-h oral glucose tolerance test. The results showed a dramatic change in glucose and lipid metabolism with age in MUL subjects...
December 2005: Diabetes
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