Natural Antisense Transcript for Hyaluronan Synthase 2 (HAS2-AS1) Induces Transcription of HAS2 via Protein O-GlcNAcylation

Vigetti, Davide; Deleonibus, Sara; Moretto, Paola; Bowen, Timothy; Fischer, Jens W.; Grandoch, Maria; Oberhuber, Alexander; Love, Dona C.; Hanover, John A.; Cinquetti, Raffaella; Karousou, Evgenia; Viola, Manuela; D’Angelo, Maria Luisa; Hascall, Vincent C.; Luca, Giancarlo De; Passi, Alberto

doi:10.1074/jbc.m114.597401

Cited by 120 publications

(108 citation statements)

References 56 publications

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“…Moreover, in MadinDarby canine kidney cells, ␤-catenin overexpression leads to the formation of a pericellular HA coat (18). In addition, coordinated induction of Has2os2 that was also dependent on LEF1 probably contributed to increased Has2 transcription, as described for human aortic smooth muscle cells (33).…”

Section: Discussionmentioning

confidence: 97%

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Esophageal Squamous Cell Carcinoma Cells Modulate Chemokine Expression and Hyaluronan Synthesis in Fibroblasts

Kretschmer

Freudenberger

Twarock

et al. 2016

Journal of Biological Chemistry

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The aim of this study was to characterize the interaction of KYSE-410, an esophageal squamous cell carcinoma cell line, and fibroblasts with respect to the extracellular matrix component hyaluronan (HA) and chemokine expression. KYSE-410 cells induced the mRNA expression of HA synthase 2 (Has2) in normal skin fibroblasts (SF) only in direct co-cultures. Parallel to Has2 mRNA, Has2 antisense RNA (Has2os2) was up-regulated in co-cultures. Knockdown of LEF1, a downstream target of Wnt signaling, abrogated Has2 and Has2os2 induction. After knockdown of Has2 in SF, significantly less ␣-smooth muscle actin expression was detected in co-cultures. Moreover, it was investigated whether the phenotype of KYSE-410 was affected in co-culture with SF and whether Has2 knockdown in SF had an impact on KYSE-410 cells in co-culture. However, no effects on epithelial-mesenchymal transition markers, proliferation, and migration were detected. In addition to Has2 mRNA, the chemokine CCL5 was up-regulated and CCL11 was down-regulated in SF in co-culture. Furthermore, co-cultures of KYSE-410 cells and cancer-associated fibroblasts (CAF) were investigated. Similar to SF, Has2 and Ccl5 were up-regulated and Ccl11 was down-regulated in CAF in co-culture. Importantly and in contrast to SF, inhibiting HA synthesis by 4-methylumbelliferone abrogated the effect of co-culture on Ccl5 in CAF. Moreover, HA was found to promote adhesion of CD4 ؉ but not CD8 ؉ cells to xenogaft tumor tissues. In conclusion, direct co-culture of esophageal squamous cell carcinoma and fibroblasts induced stromal HA synthesis via Wnt/LEF1 and altered the chemokine profile of stromal fibroblasts, which in turn may affect the tumor immune response.

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Section: Discussionmentioning

confidence: 97%

“…Recently, HAS2 antisense RNA was reported to increase HAS2 transcription in human aortic smooth muscle cells (33). The online database Ensembl (30) describes three Has2 opposite strand transcripts (Has2os1, -2, and -3) for murine Has2.…”

Section: Lef1 Was Required For Has2 Up-regulation In Sf-mentioning

confidence: 99%

Esophageal Squamous Cell Carcinoma Cells Modulate Chemokine Expression and Hyaluronan Synthesis in Fibroblasts

Kretschmer

Freudenberger

Twarock

et al. 2016

Journal of Biological Chemistry

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“…Several studies have found evidence of epigenetic changes that alter cardiometabolic disease risk, [139][140][141] including defects in endothelial cell function, abnormal blood flow, inflammation, and plaque formation. [142][143][144][145][146][147] Identification and characterization of common epigenetic outcomes linked to disease manifestations and their interaction with nutrient status may allow the development of specific treatment and intervention measures. [148][149][150][151] Interestingly, the effect of limited or oversaturated nutrient bioavailability on epigenetic states is complex and not necessarily direct.…”

Section: Role Of Nutrition In Epigenetic Perturbationmentioning

confidence: 99%

Nutrigenomics, the Microbiome, and Gene-Environment Interactions: New Directions in Cardiovascular Disease Research, Prevention, and Treatment

Ferguson¹,

Allayee²,

Gerszten³

et al. 2016

Circ Cardiovasc Genet

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Abstract-Cardiometabolic diseases are the leading cause of death worldwide and are strongly linked to both genetic and nutritional factors. The field of nutrigenomics encompasses multiple approaches aimed at understanding the effects of diet on health or disease development, including nutrigenetic studies investigating the relationship between genetic variants and diet in modulating cardiometabolic risk, as well as the effects of dietary components on multiple "omic" measures, including transcriptomics, metabolomics, proteomics, lipidomics, epigenetic modifications, and the microbiome. Here, we describe the current state of the field of nutrigenomics with respect to cardiometabolic disease research and outline a direction for the integration of multiple omics techniques in future nutrigenomic studies aimed at understanding mechanisms and developing new therapeutic options for cardiometabolic disease treatment and prevention. The interpretation and scope of nutrigenomics may vary, but it can be thought to encompass the spectrum of nutritional genomics research, including classic nutrigenetics studies of gene-diet interactions and molecular nutrition, in vitro and in vivo models, human nutrition studies, and the application of largescale, unbiased studies using high-throughput "omics" techniques to study the effects of nutrients on the body. 6 As the Figure shows, diet and the genome may influence cardiometabolic health through a variety of interconnected intermediates, perturbations in which can be measured through omics technologies, including RNA expression (transcriptome), epigenetic modifications (epigenome), metabolites (metabolome), lipids (lipidome), proteins (proteome), and resident microbial communities (microbiome). Although it is clear that both nutrients and genes play a distinct role in determining health, the complex interactions among genes, diet, and downstream networks are not well understood. The application of nutrigenomics approaches to questions of human health and disease is an important component in understanding the complexities of the interplay between basic metabolic processes and externalThe American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel. Specifically, all members of the writing group are required to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest.This statement was approved by the American Heart Association Science Advisory and Coordinating Committee on January 22, 2016, and the American Heart Association Executive Committee on February 23, 2016. A copy of the document is available at http://professional.heart.org/statements by using either "Search for Guidelines & Statements" or the "Browse by Topic" area. To purchase additional reprints, call 843-216-2533 or e-mail kelle.ramsay@ wolterskluwer.com.The...

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“…It is important to ask patients whether they are taking their medications and to encourage continued and appropriate compliance with their osteoporosis therapies to reduce fracture risk. Physical medicine and rehabilitation can reduce disability, improve physical function and lower the risk of subsequent falls in patients with osteoporosis 10 .…”

Section: Proceedings Of the XXXV National Meeting Of The Italian Socimentioning

confidence: 99%

“…O-GlcNAcylation of HAS2 is present on serine 221 residue that induces a dramatic stabilization of the enzyme in the membranes increasing HA production 9 . Eventually we found a long non-coding RNA (NAT) for HAS2, which plays a role in this context involving p65 and NFkB pathway as ChIP analysis 10,11 . Unpublished data revealed that oxLDL are able to induce an increase of NAT for HAS2 in smooth muscle cells as well as other epigenetic modifications induced by P300 activity.…”

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confidence: 99%

Proceedings of the XXXV National Meeting of the Italian Society for the Study of Connective Tissues (SISC)

Rossi¹

2015

Eur J Histochem

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Natural Antisense Transcript for Hyaluronan Synthase 2 (HAS2-AS1) Induces Transcription of HAS2 via Protein O-GlcNAcylation

Cited by 120 publications

References 56 publications

Esophageal Squamous Cell Carcinoma Cells Modulate Chemokine Expression and Hyaluronan Synthesis in Fibroblasts

Esophageal Squamous Cell Carcinoma Cells Modulate Chemokine Expression and Hyaluronan Synthesis in Fibroblasts

Nutrigenomics, the Microbiome, and Gene-Environment Interactions: New Directions in Cardiovascular Disease Research, Prevention, and Treatment

Proceedings of the XXXV National Meeting of the Italian Society for the Study of Connective Tissues (SISC)

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