scholarly journals RNA-directed epigenetic silencing of Periostin inhibits cell motility

2015 ◽  
Vol 2 (6) ◽  
pp. 140545 ◽  
Author(s):  
Nicholas C. Lister ◽  
Matthew Clemson ◽  
Kevin V. Morris
Keyword(s):  
Cell Cycle ◽  
Extracellular Matrix ◽  
Cell Motility ◽  
Epigenetic Regulation ◽  
Epigenetic Silencing ◽  
Transcriptional Gene Silencing ◽  
Cellular Motility ◽  
Over Expression ◽  
Non Coding Rnas ◽  
Cancerous Cells

The over-expression of Periostin, a member of the fasciclin family of proteins, has been reported in a number of cancers and, in particular, in metastatic tumours. These include breast, ovarian, lung, colon, head and neck, pancreatic, prostate, neuroblastoma and thyroid cancers. It is thought that Periostin plays a major role in the development of metastases owing to its apparent involvement in restructuring of the extracellular matrix to create a microenvironment favouring invasion and metastases, angiogenesis, independent proliferation, avoidance of apoptosis and the ability for cells to re-enter the cell cycle. As such we reasoned that targeted suppression of Periostin at the promoter and epigenetic level could result in the stable inhibition of cell motility. We find here that promoter-directed small antisense non-coding RNAs can induce transcriptional gene silencing of Periostin that results ultimately in a loss of cellular motility. The observations presented here suggest that cell motility and possibly metastasis can be controlled by transcriptional and epigenetic regulation of Periostin, offering a potentially new and novel manner to control the spread of cancerous cells.

scholarly journals Dynamics of filopodium-like protrusion and endothelial cellular motility on one-dimensional extracellular matrix fibrils

2014 ◽  
Vol 4 (2) ◽  
pp. 20130060 ◽  
Author(s):  
Niannan Xue ◽  
Cristina Bertulli ◽  
Amine Sadok ◽  
Yan Yan Shery Huang
Keyword(s):  
Extracellular Matrix ◽  
Endothelial Cells ◽  
Cell Motility ◽  
Near Field ◽  
Morphological Characteristics ◽  
Morphological Parameters ◽  
Cellular Motility ◽  
One Dimensional ◽  
Rock Inhibition

Endothelial filopodia play key roles in guiding the tubular sprouting during angiogenesis. However, their dynamic morphological characteristics, with the associated implications in cell motility, have been subjected to limited investigations. In this work, the interaction between endothelial cells and extracellular matrix fibrils was recapitulated in vitro , where a specific focus was paid to derive the key morphological parameters to define the dynamics of filopodium-like protrusion during cell motility. Based on one-dimensional gelatin fibrils patterned by near-field electrospinning (NFES), we study the response of endothelial cells (EA.hy926) under normal culture or ROCK inhibition. It is shown that the behaviour of temporal protrusion length versus cell motility can be divided into distinct modes. Persistent migration was found to be one of the modes which permitted cell displacement for over 300 µm at a speed of approximately 1 µm min −1 . ROCK inhibition resulted in abnormally long protrusions and diminished the persistent migration, but dramatically increased the speeds of protrusion extension and retraction. Finally, we also report the breakage of protrusion during cell motility, and examine its phenotypic behaviours.

scholarly journals The Epigenetic Regulation of Microenvironment in Hepatocellular Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Fang Wang ◽  
Greg Malnassy ◽  
Wei Qiu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Dna Methylation ◽  
Extracellular Matrix ◽  
Endothelial Cells ◽  
Tumor Microenvironment ◽  
Epigenetic Regulation ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Epigenetic Mechanisms ◽  
Non Coding Rnas

Hepatocellular carcinoma (HCC) is a highly lethal and complex malignancy strongly influenced by the surrounding tumor microenvironment. The HCC microenvironment comprises hepatic stellate cells (HSCs), tumor-associated macrophages (TAMs), stromal and endothelial cells, and the underlying extracellular matrix (ECM). Emerging evidence demonstrates that epigenetic regulation plays a crucial role in altering numerous components of the HCC tumor microenvironment. In this review, we summarize the current understanding of the mechanisms of epigenetic regulation of the microenvironment in HCC. We review recent studies demonstrating how specific epigenetic mechanisms (DNA methylation, histone regulation, and non-coding RNAs mediated regulation) in HSCs, TAMs, and ECM, and how they contribute to HCC development, so as to gain new insights into the treatment of HCC via regulating epigenetic regulation in the tumor microenvironment.

scholarly journals Retinoblastoma Tumor Suppressor Protein Roles in Epigenetic Regulation

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2807
Author(s):  
Frederick Guzman ◽  
Yasamin Fazeli ◽  
Meagan Khuu ◽  
Kelsey Salcido ◽  
Sarah Singh ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Epigenetic Regulation ◽  
Cell Cycle Progression ◽  
Cell Cycle Exit ◽  
Loss Of Function ◽  
Cycle Progression ◽  
Retinoblastoma Tumor Suppressor Protein ◽  
Retinoblastoma Tumor Suppressor ◽  
Non Coding Rnas ◽  
Retinoblastoma Tumor

Mutations that result in the loss of function of pRB were first identified in retinoblastoma and since then have been associated with the propagation of various forms of cancer. pRB is best known for its key role as a transcriptional regulator during cell cycle exit. Beyond the ability of pRB to regulate transcription of cell cycle progression genes, pRB can remodel chromatin to exert several of its other biological roles. In this review, we discuss the diverse functions of pRB in epigenetic regulation including nucleosome mobilization, histone modifications, DNA methylation and non-coding RNAs.

Tubulin Proteins in Cancer Resistance: A Review

2020 ◽  
Vol 21 (3) ◽  
pp. 178-185 ◽  
Author(s):  
Mohammad Amjad Kamal ◽  
Maryam Hassan Al-Zahrani ◽  
Salman Hasan Khan ◽  
Mateen Hasan Khan ◽  
Hani Awad Al-Subhi ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cancer Cells ◽  
High Rate ◽  
Vinca Alkaloids ◽  
Cancer Resistance ◽  
New Approach ◽  
Natural Sources ◽  
Cell Cycle Genes ◽  
Cancerous Cells ◽  
Β Tubulin

Cancer cells are altered with cell cycle genes or they are mutated, leading to a high rate of proliferation compared to normal cells. Alteration in these genes leads to mitosis dysregulation and becomes the basis of tumor progression and resistance to many drugs. The drugs which act on the cell cycle fail to arrest the process, making cancer cell non-responsive to apoptosis or cell death. Vinca alkaloids and taxanes fall in this category and are referred to as antimitotic agents. Microtubule proteins play an important role in mitosis during cell division as a target site for vinca alkaloids and taxanes. These proteins are dynamic in nature and are composed of α-β-tubulin heterodimers. β-tubulin specially βΙΙΙ isotype is generally altered in expression within cancerous cells. Initially, these drugs were very effective in the treatment of cancer but failed to show their desired action after initial chemotherapy. The present review highlights some of the important targets and their mechanism of resistance offered by cancer cells with new promising drugs from natural sources that can lead to the development of a new approach to chemotherapy.

scholarly journals Bmi1 Augments Proliferation and Survival of Cortical Bone-Derived Stem Cells after Injury through Novel Epigenetic Signaling via Histone 3 Regulation

2021 ◽  
Vol 22 (15) ◽  
pp. 7813
Author(s):  
Lindsay Kraus ◽  
Chris Bryan ◽  
Marcus Wagner ◽  
Tabito Kino ◽  
Melissa Gunchenko ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Dna Damage ◽  
Stem Cell ◽  
Histone Modification ◽  
Epigenetic Regulation ◽  
Critical Role ◽  
Proliferative Potential ◽  
Therapeutic Effects ◽  
Histone 3

Ischemic heart disease can lead to myocardial infarction (MI), a major cause of morbidity and mortality worldwide. Multiple stem cell types have been safely transferred into failing human hearts, but the overall clinical cardiovascular benefits have been modest. Therefore, there is a dire need to understand the basic biology of stem cells to enhance therapeutic effects. Bmi1 is part of the polycomb repressive complex 1 (PRC1) that is involved in different processes including proliferation, survival and differentiation of stem cells. We isolated cortical bones stem cells (CBSCs) from bone stroma, and they express significantly high levels of Bmi1 compared to mesenchymal stem cells (MSCs) and cardiac-derived stem cells (CDCs). Using lentiviral transduction, Bmi1 was knocked down in the CBSCs to determine the effect of loss of Bmi1 on proliferation and survival potential with or without Bmi1 in CBSCs. Our data show that with the loss of Bmi1, there is a decrease in CBSC ability to proliferate and survive during stress. This loss of functionality is attributed to changes in histone modification, specifically histone 3 lysine 27 (H3K27). Without the proper epigenetic regulation, due to the loss of the polycomb protein in CBSCs, there is a significant decrease in cell cycle proteins, including Cyclin B, E2F, and WEE as well as an increase in DNA damage genes, including ataxia-telangiectasia mutated (ATM) and ATM and Rad3-related (ATR). In conclusion, in the absence of Bmi1, CBSCs lose their proliferative potential, have increased DNA damage and apoptosis, and more cell cycle arrest due to changes in epigenetic modifications. Consequently, Bmi1 plays a critical role in stem cell proliferation and survival through cell cycle regulation, specifically in the CBSCs. This regulation is associated with the histone modification and regulation of Bmi1, therefore indicating a novel mechanism of Bmi1 and the epigenetic regulation of stem cells.

scholarly journals The activity status of cofilin is directly related to invasion, intravasation, and metastasis of mammary tumors

2006 ◽  
Vol 173 (3) ◽  
pp. 395-404 ◽  
Author(s):  
Weigang Wang ◽  
Ghassan Mouneimne ◽  
Mazen Sidani ◽  
Jeffrey Wyckoff ◽  
Xiaoming Chen ◽  
...  
Keyword(s):  
Cell Motility ◽  
Cell Invasion ◽  
Actin Polymerization ◽  
Cancer Cell Invasion ◽  
Invasion And Metastasis ◽  
Over Expression ◽  
Cell Biol ◽  
Tumor Cell Motility ◽  
New Strategies

Understanding the mechanisms controlling cancer cell invasion and metastasis constitutes a fundamental step in setting new strategies for diagnosis, prognosis, and therapy of metastatic cancers. LIM kinase1 (LIMK1) is a member of a novel class of serine–threonine protein kinases. Cofilin, a LIMK1 substrate, is essential for the regulation of actin polymerization and depolymerization during cell migration. Previous studies have made opposite conclusions as to the role of LIMK1 in tumor cell motility and metastasis, claiming either an increase or decrease in cell motility and metastasis as a result of LIMK1 over expression (Zebda, N., O. Bernard, M. Bailly, S. Welti, D.S. Lawrence, and J.S. Condeelis. 2000. J. Cell Biol. 151:1119–1128; Davila, M., A.R. Frost, W.E. Grizzle, and R. Chakrabarti. 2003. J. Biol. Chem. 278:36868–36875; Yoshioka, K., V. Foletta, O. Bernard, and K. Itoh. 2003. Proc. Natl. Acad. Sci. USA. 100:7247–7252; Nishita, M., C. Tomizawa, M. Yamamoto, Y. Horita, K. Ohashi, and K. Mizuno. 2005. J. Cell Biol. 171:349–359). We resolve this paradox by showing that the effects of LIMK1 expression on migration, intravasation, and metastasis of cancer cells can be most simply explained by its regulation of the output of the cofilin pathway. LIMK1-mediated decreases or increases in the activity of the cofilin pathway are shown to cause proportional decreases or increases in motility, intravasation, and metastasis of tumor cells.

Cell motility and the extracellular matrix

1990 ◽  
Vol 2 (5) ◽  
pp. 850-856 ◽  
Author(s):  
B.R. Zetter ◽  
S.E. Brightman
Keyword(s):  
Extracellular Matrix ◽  
Cell Motility

scholarly journals Modulation of Cellular Migration and Survival by c-Myc through the Downregulation of Urokinase (uPA) and uPA Receptor

2010 ◽  
Vol 30 (7) ◽  
pp. 1838-1851 ◽  
Author(s):  
Daniela Alfano ◽  
Giuseppina Votta ◽  
Almut Schulze ◽  
Julian Downward ◽  
Mario Caputi ◽  
...  
Keyword(s):  
Cell Motility ◽  
Cellular Transformation ◽  
Tumor Formation ◽  
Cellular Migration ◽  
Epithelial Cell Line ◽  
Cellular Motility ◽  
Upa Receptor ◽  
Upar Expression ◽  
Repressive Effect ◽  
Cell Invasiveness

ABSTRACT It has been proposed that c-Myc proapoptotic activity accounts for most of its restraint of tumor formation. We established a telomerase-immortalized human epithelial cell line expressing an activatable c-Myc protein. We found that c-Myc activation induces, in addition to increased sensitivity to apoptosis, reductions in cell motility and invasiveness. Transcriptome analysis revealed that urokinase (uPA) and uPA receptor (uPAR) were strongly downregulated by c-Myc. Evidence is provided that the repression of uPA and uPAR may account for most of the antimigratory and proapoptotic activities of c-Myc. c-Myc is known to cooperate with Ras in cellular transformation. We therefore investigated if this cooperation could converge in the control of uPA/uPAR expression. We found that Ras is able to block the effects of c-Myc activation on apoptosis and cellular motility but not on cell invasiveness. Accordingly, the activation of c-Myc in the context of Ras expression had only minor influence on uPAR expression but still had a profound repressive effect on uPA expression. Thus, the differential regulation of uPA and uPAR by c-Myc and Ras correlates with the effects of these two oncoproteins on cell motility, invasiveness, and survival. In conclusion, we have discovered a novel link between c-Myc and uPA/uPAR. We propose that reductions of cell motility and invasiveness could contribute to the inhibition of tumorigenesis by c-Myc and that the regulation of uPA and uPAR expression may be a component of the ability of c-Myc to reduce motility and invasiveness.

scholarly journals Extracellular Vesicles and Matrix Remodeling Enzymes: The Emerging Roles in Extracellular Matrix Remodeling, Progression of Diseases and Tissue Repair

Cells ◽  
2018 ◽  
Vol 7 (10) ◽  
pp. 167 ◽  
Author(s):  
Muhammad Nawaz ◽  
Neelam Shah ◽  
Bruna Zanetti ◽  
Marco Maugeri ◽  
Renata Silvestre ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Extracellular Vesicles ◽  
Tissue Repair ◽  
Metabolic Diseases ◽  
Bioactive Molecules ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Matrix Remodeling ◽  
Pathological Conditions ◽  
Potential Applications ◽  
Non Coding Rnas

Extracellular vesicles (EVs) are membrane enclosed micro- and nano-sized vesicles that are secreted from almost every species, ranging from prokaryotes to eukaryotes, and from almost every cell type studied so far. EVs contain repertoire of bioactive molecules such as proteins (including enzymes and transcriptional factors), lipids, carbohydrates and nucleic acids including DNA, coding and non-coding RNAs. The secreted EVs are taken up by neighboring cells where they release their content in recipient cells, or can sail through body fluids to reach distant organs. Since EVs transport bioactive cargo between cells, they have emerged as novel mediators of extra- and intercellular activities in local microenvironment and inter-organ communications distantly. Herein, we review the activities of EV-associated matrix-remodeling enzymes such as matrix metalloproteinases, heparanases, hyaluronidases, aggrecanases, and their regulators such as extracellular matrix metalloproteinase inducers and tissue inhibitors of metalloproteinases as novel means of matrix remodeling in physiological and pathological conditions. We discuss how such EVs act as novel mediators of extracellular matrix degradation to prepare a permissive environment for various pathological conditions such as cancer, cardiovascular diseases, arthritis and metabolic diseases. Additionally, the roles of EV-mediated matrix remodeling in tissue repair and their potential applications as organ therapies have been reviewed. Collectively, this knowledge could benefit the development of new approaches for tissue engineering.

scholarly journals Joint changes in RNA, RNA polymerase II, and promoter activity through the cell cycle identify non-coding RNAs involved in proliferation

2021 ◽  
Author(s):  
Siv Anita Hegre ◽  
Helle Samdal ◽  
Antonin Klima ◽  
Endre B. Stovner ◽  
Kristin G. Nørsett ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Promoter Activity ◽  
Cycle Phase ◽  
Specific Expression ◽  
Chip Sequencing ◽  
Non Coding Rnas ◽  
Cycle Dependent ◽  
Rna Levels

AbstractProper regulation of the cell cycle is necessary for normal growth and development of all organisms. Conversely, altered cell cycle regulation often underlies proliferative diseases such as cancer. Long non-coding RNAs (lncRNAs) are recognized as important regulators of gene expression and are often found dysregulated in diseases, including cancers. However, identifying lncRNAs with cell cycle functions is challenging due to their often low and cell-type specific expression. We present a highly effective method that analyses changes in promoter activity, transcription, and RNA levels for identifying genes enriched for cell cycle functions. Specifically, by combining RNA sequencing with ChIP sequencing through the cell cycle of synchronized human keratinocytes, we identified 1009 genes with cell cycle-dependent expression and correlated changes in RNA polymerase II occupancy or promoter activity as measured by histone 3 lysine 4 trimethylation (H3K4me3). These genes were highly enriched for genes with known cell cycle functions and included 59 lncRNAs. We selected four of these lncRNAs – AC005682.5, RP11-132A1.4, ZFAS1, and EPB41L4A-AS1 – for further experimental validation and found that knockdown of each of the four lncRNAs affected cell cycle phase distributions and reduced proliferation in multiple cell lines. These results show that many genes with cell cycle functions have concomitant cell-cycle dependent changes in promoter activity, transcription, and RNA levels and support that our multi-omics method is well suited for identifying lncRNAs involved in the cell cycle.

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