Genes

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Open AccessReview

Role of Telomerase in the Cardiovascular System

by Mark Zurek, Joachim Altschmied, Stefanie Kohlgrüber, Niloofar Ale-Agha and Judith Haendeler

Genes 2016, 7(6), 29; https://doi.org/10.3390/genes7060029 - 17 Jun 2016

Cited by 27 | Viewed by 6597

Aging is one major risk factor for the incidence of cardiovascular diseases and the development of atherosclerosis. One important enzyme known to be involved in aging processes is Telomerase Reverse Transcriptase (TERT). After the discovery of the enzyme in humans, TERT had initially [...] Read more.

Aging is one major risk factor for the incidence of cardiovascular diseases and the development of atherosclerosis. One important enzyme known to be involved in aging processes is Telomerase Reverse Transcriptase (TERT). After the discovery of the enzyme in humans, TERT had initially only been attributed to germ line cells, stem cells and cancer cells. However, over the last few years it has become clear that TERT is also active in cells of the cardiovascular system including cardiac myocytes, endothelial cells, smooth muscle cells and fibroblasts. Interference with the activity of this enzyme greatly contributes to cardiovascular diseases. This review will summarize the findings on the role of TERT in cardiovascular cells. Moreover, recent findings concerning TERT in different mouse models with respect to cardiovascular diseases will be described. Finally, the extranuclear functions of TERT will be covered within this review. Full article

(This article belongs to the Special Issue Telomerase Activity in Human Cells)

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Open AccessReview

The MST/Hippo Pathway and Cell Death: A Non-Canonical Affair

by Emma Fallahi, Niamh A. O’Driscoll and David Matallanas

Genes 2016, 7(6), 28; https://doi.org/10.3390/genes7060028 - 17 Jun 2016

Cited by 67 | Viewed by 11321

Abstract

The MST/Hippo signalling pathway was first described over a decade ago in Drosophila melanogaster and the core of the pathway is evolutionary conserved in mammals. The mammalian MST/Hippo pathway regulates organ size, cell proliferation and cell death. In addition, it has been shown [...] Read more.

The MST/Hippo signalling pathway was first described over a decade ago in Drosophila melanogaster and the core of the pathway is evolutionary conserved in mammals. The mammalian MST/Hippo pathway regulates organ size, cell proliferation and cell death. In addition, it has been shown to play a central role in the regulation of cellular homeostasis and it is commonly deregulated in human tumours. The delineation of the canonical pathway resembles the behaviour of the Hippo pathway in the fly where the activation of the core kinases of the pathway prevents the proliferative signal mediated by the key effector of the pathway YAP. Nevertheless, several lines of evidence support the idea that the mammalian MST/Hippo pathway has acquired new features during evolution, including different regulators and effectors, crosstalk with other essential signalling pathways involved in cellular homeostasis and the ability to actively trigger cell death. Here we describe the current knowledge of the mechanisms that mediate MST/Hippo dependent cell death, especially apoptosis. We include evidence for the existence of complex signalling networks where the core proteins of the pathway play a central role in controlling the balance between survival and cell death. Finally, we discuss the possible involvement of these signalling networks in several human diseases such as cancer, diabetes and neurodegenerative disorders. Full article

(This article belongs to the Special Issue Hippo Signaling Pathway)

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Open AccessArticle

Telomerase Activity is Downregulated Early During Human Brain Development

by Abbas Ishaq, Peter S. Hanson, Christopher M. Morris and Gabriele Saretzki

Genes 2016, 7(6), 27; https://doi.org/10.3390/genes7060027 - 16 Jun 2016

Cited by 25 | Viewed by 6559

Abstract

Changes in hTERT splice variant expression have been proposed to facilitate the decrease of telomerase activity during fetal development in various human tissues. Here, we analyzed the expression of telomerase RNA (hTR), wild type and α-spliced hTERT in developing human fetal brain (post [...] Read more.

Changes in hTERT splice variant expression have been proposed to facilitate the decrease of telomerase activity during fetal development in various human tissues. Here, we analyzed the expression of telomerase RNA (hTR), wild type and α-spliced hTERT in developing human fetal brain (post conception weeks, pcw, 6–19) and in young and old cortices using qPCR and correlated it to telomerase activity measured by TRAP assay. Decrease of telomerase activity occurred early during brain development and correlated strongest to decreased hTR expression. The expression of α-spliced hTERT increased between pcw 10 and 19, while that of wild type hTERT remained unchanged. Lack of expression differences between young and old cortices suggests that most changes seem to occur early during human brain development. Using in vitro differentiation of neural precursor stem cells (NPSCs) derived at pcw 6 we found a decrease in telomerase activity but no major expression changes in telomerase associated genes. Thus, they do not seem to model the mechanisms for the decrease in telomerase activity in fetal brains. Our results suggest that decreased hTR levels, as well as transient increase in α-spliced hTERT, might both contribute to downregulation of telomerase activity during early human brain development between 6 and 17 pcw. Full article

(This article belongs to the Special Issue Telomerase Activity in Human Cells)

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Open AccessArticle

A Multi-Step miRNA-mRNA Regulatory Network Construction Approach Identifies Gene Signatures Associated with Endometrioid Endometrial Carcinoma

by Hanzhen Xiong, Qiulian Li, Ruichao Chen, Shaoyan Liu, Qiongyan Lin, Zhongtang Xiong, Qingping Jiang and Linlang Guo

Genes 2016, 7(6), 26; https://doi.org/10.3390/genes7060026 - 2 Jun 2016

Cited by 7 | Viewed by 4878

Abstract

We aimed to identify endometrioid endometrial carcinoma (EEC)-related gene signatures using a multi-step miRNA-mRNA regulatory network construction approach. Pathway analysis showed that 61 genes were enriched on many carcinoma-related pathways. Among the 14 highest scoring gene signatures, six genes had been previously shown [...] Read more.

We aimed to identify endometrioid endometrial carcinoma (EEC)-related gene signatures using a multi-step miRNA-mRNA regulatory network construction approach. Pathway analysis showed that 61 genes were enriched on many carcinoma-related pathways. Among the 14 highest scoring gene signatures, six genes had been previously shown to be endometrial carcinoma. By qRT-PCR and next generation sequencing, we found that a gene signature (CPEB1) was significantly down-regulated in EEC tissues, which may be caused by hsa-miR-183-5p up-regulation. In addition, our literature surveys suggested that CPEB1 may play an important role in EEC pathogenesis by regulating the EMT/p53 pathway. The miRNA-mRNA network is worthy of further investigation with respect to the regulatory mechanisms of miRNAs in EEC. CPEB1 appeared to be a tumor suppressor in EEC. Our results provided valuable guidance for the functional study at the cellular level, as well as the EEC mouse models. Full article

(This article belongs to the Section Human Genomics and Genetic Diseases)

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Open AccessTechnical Note

Selection and Verification of Candidate Reference Genes for Mature MicroRNA Expression by Quantitative RT-PCR in the Tea Plant (Camellia sinensis)

by Hui Song, Xiao Zhang, Cong Shi, Shuangshuang Wang, Ailin Wu and Chaoling Wei

Genes 2016, 7(6), 25; https://doi.org/10.3390/genes7060025 - 28 May 2016

Cited by 36 | Viewed by 6052

Abstract

Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) is a rapid and sensitive method for analyzing microRNA (miRNA) expression. However, accurate qRT-PCR results depend on the selection of reliable reference genes as internal positive controls. To date, few studies have identified reliable reference genes for [...] Read more.

Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) is a rapid and sensitive method for analyzing microRNA (miRNA) expression. However, accurate qRT-PCR results depend on the selection of reliable reference genes as internal positive controls. To date, few studies have identified reliable reference genes for differential expression analysis of miRNAs among tissues, and among experimental conditions in plants. In this study, three miRNAs and four non-coding small RNAs (ncRNA) were selected as reference candidates, and the stability of their expression was evaluated among different tissues and under different experimental conditions in the tea plant (Camellia sinensis) using the geNorm and NormFinder programs. It was shown that miR159a was the best single reference gene in the bud to the fifth leaf, 5S rRNA was the most suitable gene in different organs, miR6149 was the most stable gene when the leaves were attacked by Ectropis oblique and U4, miR5368n and miR159a were the best genes when the leaves were treated by methyl jasmonate (MeJA), salicylic acid (SA) and abscisic acid (ABA), respectively. Our results provide suitable reference genes for future investigations on miRNA functions in tea plants. Full article

(This article belongs to the Section Population and Evolutionary Genetics and Genomics)

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Open AccessReview

Wool Keratin-Associated Protein Genes in Sheep—A Review

by Hua Gong, Huitong Zhou, Rachel H. J. Forrest, Shaobin Li, Jiqing Wang, Jolon M. Dyer, Yuzhu Luo and Jon G. H. Hickford

Genes 2016, 7(6), 24; https://doi.org/10.3390/genes7060024 - 28 May 2016

Cited by 92 | Viewed by 10299

Abstract

The importance of sheep’s wool in making textiles has inspired extensive research into its structure and the underlying genetics since the 1960s. Wool keratin-associated proteins (KAPs) are a key structural component of the wool fibre. The characterisation of the genes encoding these proteins [...] Read more.

The importance of sheep’s wool in making textiles has inspired extensive research into its structure and the underlying genetics since the 1960s. Wool keratin-associated proteins (KAPs) are a key structural component of the wool fibre. The characterisation of the genes encoding these proteins has progressed rapidly with advances in the nucleotide and protein sequencing. This review describes our knowledge of ovine KAPs, their categorisation into families, polymorphism in the proteins and genes, the clustering and chromosomal location of the genes, some characteristics of gene expression and some potential effects of the KAPs on wool traits. The extent and nature of genetic variation in wool KAP genes and its association with fibre characteristics, provides an opportunity for the development of gene-markers for selective breeding of sheep to produce better wool with properties highly matched to specific end-uses. Full article

(This article belongs to the Section Population and Evolutionary Genetics and Genomics)

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Open AccessReview

The Regulatory Role of KIBRA and PTPN14 in Hippo Signaling and Beyond

by Kayla E. Wilson, Nuo Yang, Ashley L. Mussell and Jianmin Zhang

Genes 2016, 7(6), 23; https://doi.org/10.3390/genes7060023 - 27 May 2016

Cited by 30 | Viewed by 5947

Abstract

The Hippo signaling pathway regulates cellular proliferation and survival, thus exerting profound effects on normal cell fate and tumorigenesis. Pivotal effectors of this pathway are YAP/TAZ, transcriptional co-activators whose dysfunction contributes to the development of cancer. Complex networks of intracellular and extracellular signaling [...] Read more.

The Hippo signaling pathway regulates cellular proliferation and survival, thus exerting profound effects on normal cell fate and tumorigenesis. Pivotal effectors of this pathway are YAP/TAZ, transcriptional co-activators whose dysfunction contributes to the development of cancer. Complex networks of intracellular and extracellular signaling pathways that modulate YAP and TAZ activities have recently been identified. Among them, KIBRA and PTPN14 are two evolutionarily-conserved and important YAP/TAZ upstream regulators. They can negatively regulate YAP/TAZ functions separately or in concert. In this review, we summarize the current and emerging regulatory roles of KIBRA and PTPN14 in the Hippo pathway and their functions in cancer. Full article

(This article belongs to the Special Issue Hippo Signaling Pathway)

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Open AccessReview

Telomere and Telomerase Therapeutics in Cancer

by Yucheng Xu and Amir Goldkorn

Genes 2016, 7(6), 22; https://doi.org/10.3390/genes7060022 - 26 May 2016

Cited by 82 | Viewed by 9425

Abstract

Telomerase is a reverse transcriptase capable of utilizing an integrated RNA component as a template to add protective tandem telomeric single strand DNA repeats, TTAGGG, to the ends of chromosomes. Telomere dysfunction and telomerase reactivation are observed in approximately 90% of human cancers; [...] Read more.

Telomerase is a reverse transcriptase capable of utilizing an integrated RNA component as a template to add protective tandem telomeric single strand DNA repeats, TTAGGG, to the ends of chromosomes. Telomere dysfunction and telomerase reactivation are observed in approximately 90% of human cancers; hence, telomerase activation plays a unique role as a nearly universal step on the path to malignancy. In the past two decades, multiple telomerase targeting therapeutic strategies have been pursued, including direct telomerase inhibition, telomerase interference, hTERT or hTERC promoter driven therapy, telomere-based approaches, and telomerase vaccines. Many of these strategies have entered clinical development, and some have now advanced to phase III clinical trials. In the coming years, one or more of these new telomerase-targeting drugs may be expected to enter the pharmacopeia of standard care. Here, we briefly review the molecular functions of telomerase in cancer and provide an update about the preclinical and clinical development of telomerase targeting therapeutics. Full article

(This article belongs to the Special Issue Telomerase Activity in Human Cells)

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Genes, Volume 7, Issue 6 (June 2016) – 8 articles

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