scholarly journals Non-coding RNAs: emerging players in cardiomyocyte proliferation and cardiac regeneration

2020 ◽  
Vol 115 (5) ◽  
Author(s):  
Naisam Abbas ◽  
Filippo Perbellini ◽  
Thomas Thum
Keyword(s):  
Cell Cycle ◽  
Molecular Mechanisms ◽  
Contractile Function ◽  
Cardiac Regeneration ◽  
Therapeutic Interventions ◽  
Circular Rnas ◽  
Cardiomyocyte Proliferation ◽  
Protein Coding ◽  
Rna Molecules ◽  
Non Coding Rnas

Abstract Soon after birth, the regenerative capacity of the mammalian heart is lost, cardiomyocytes withdraw from the cell cycle and demonstrate a minimal proliferation rate. Despite improved treatment and reperfusion strategies, the uncompensated cardiomyocyte loss during injury and disease results in cardiac remodeling and subsequent heart failure. The promising field of regenerative medicine aims to restore both the structure and function of damaged tissue through modulation of cellular processes and regulatory mechanisms involved in cardiac cell cycle arrest to boost cardiomyocyte proliferation. Non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) are functional RNA molecules with no protein-coding function that have been reported to engage in cardiac regeneration and repair. In this review, we summarize the current understanding of both the biological functions and molecular mechanisms of ncRNAs involved in cardiomyocyte proliferation. Furthermore, we discuss their impact on the structure and contractile function of the heart in health and disease and their application for therapeutic interventions.

scholarly journals Circular and long non-coding RNAs and their role in ophthalmologic diseases

2018 ◽  
Author(s):  
Olga Wawrzyniak ◽  
Żaneta Zarębska ◽  
Katarzyna Rolle ◽  
Anna Gotz-Więckowska
Keyword(s):  
Current Knowledge ◽  
Critical Role ◽  
Circular Rna ◽  
Age Related Macular Degeneration ◽  
Circular Rnas ◽  
Protein Coding ◽  
Rna Molecules ◽  
Age Related ◽  
Non Coding Rnas ◽  
Transcriptional Gene Regulation

Long non-coding RNAs are >200-nucleotide-long RNA molecules which lack or have limited protein-coding potential. They can regulate protein formation through several different mechanisms. Similarly, circular RNAs are reported to play a critical role in post-transcriptional gene regulation. Changes in the expression pattern of these molecules are known to underlie various diseases, including cancer, cardiovascular, neurological and immunological disorders (Rinn & Chang, 2012; Sun & Kraus, 2015). Recent studies suggest that they are differentially expressed both in healthy ocular tissues as well as in eye pathologies, such as neovascularization, proliferative vitreoretinopathy, glaucoma, cataract, ocular malignancy or even strabismus (Li et al., 2016). Aetiology of ocular diseases is multifactorial and combines genetic and environmental factors, including epigenetic and non-coding RNAs. In addition, disorders like diabetic retinopathy or age-related macular degeneration lack biomarkers for early detection as well as effective treatment methods that would allow controlling the disease progression at its early stages. The newly discovered non-coding RNAs seem to be the ideal candidates for novel molecular markers and therapeutic strategies. In this review, we summarized the current knowledge about gene expression regulators – long non-coding and circular RNA molecules in eye diseases.

scholarly journals Non-coding RNAs in Cardiac Regeneration

2021 ◽  
Vol 12 ◽  
Author(s):  
Ting Yuan ◽  
Jaya Krishnan
Keyword(s):  
Heart Failure ◽  
Cardiac Tissue ◽  
Cardiac Regeneration ◽  
Circular Rnas ◽  
Great Promise ◽  
Cardiomyocyte Proliferation ◽  
Non Coding Rnas ◽  
Key Aspects

The adult heart has a limited capacity to replace or regenerate damaged cardiac tissue following severe myocardial injury. Thus, therapies facilitating the induction of cardiac regeneration holds great promise for the treatment of end-stage heart failure, and for pathologies invoking severe cardiac dysfunction as a result of cardiomyocyte death. Recently, a number of studies have demonstrated that cardiac regeneration can be achieved through modulation and/or reprogramming of cardiomyocyte proliferation, differentiation, and survival signaling. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), are reported to play critical roles in regulating key aspects of cardiomyocyte physiologic and pathologic signaling, including the regulation of cardiac regeneration both in vitro and in vivo. In this review, we will explore and detail the current understanding of ncRNA function in cardiac regeneration, and highlight established and novel strategies for the treatment of heart failure through modulation of ncRNAs-driven cardiac regeneration.

Radio-Susceptibility of Nasopharyngeal Carcinoma: Focus on Epstein- Barr Virus, MicroRNAs, Long Non-Coding RNAs and Circular RNAs

2020 ◽  
Vol 13 (3) ◽  
pp. 192-205 ◽  
Author(s):  
Fanghong Lei ◽  
Tongda Lei ◽  
Yun Huang ◽  
Mingxiu Yang ◽  
Mingchu Liao ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Regulatory Networks ◽  
Epstein Barr Virus ◽  
Molecular Mechanisms ◽  
Acquired Resistance ◽  
Treatment Strategies ◽  
Circular Rnas ◽  
Barr Virus ◽  
Non Coding Rnas ◽  
Epstein Barr

Nasopharyngeal carcinoma (NPC) is a type of head and neck cancer. As a neoplastic disorder, NPC is a highly malignant squamous cell carcinoma that is derived from the nasopharyngeal epithelium. NPC is radiosensitive; radiotherapy or radiotherapy combining with chemotherapy are the main treatment strategies. However, both modalities are usually accompanied by complications and acquired resistance to radiotherapy is a significant impediment to effective NPC therapy. Therefore, there is an urgent need to discover effective radio-sensitization and radio-resistance biomarkers for NPC. Recent studies have shown that Epstein-Barr virus (EBV)-encoded products, microRNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), which share several common signaling pathways, can function in radio-related NPC cells or tissues. Understanding these interconnected regulatory networks will reveal the details of NPC radiation sensitivity and resistance. In this review, we discuss and summarize the specific molecular mechanisms of NPC radio-sensitization and radio-resistance, focusing on EBV-encoded products, miRNAs, lncRNAs and circRNAs. This will provide a foundation for the discovery of more accurate, effective and specific markers related to NPC radiotherapy. EBVencoded products, miRNAs, lncRNAs and circRNAs have emerged as crucial molecules mediating the radio-susceptibility of NPC. This understanding will improve the clinical application of markers and inform the development of novel therapeutics for NPC.

scholarly journals Hypoxia-induced myocardial regeneration

2017 ◽  
Vol 123 (6) ◽  
pp. 1676-1681 ◽  
Author(s):  
Wataru Kimura ◽  
Yuji Nakada ◽  
Hesham A. Sadek
Keyword(s):  
Oxidative Stress ◽  
Cell Cycle ◽  
Systolic Heart Failure ◽  
Cardiac Regeneration ◽  
Oxygen Metabolism ◽  
Functional Improvement ◽  
Cardiomyocyte Proliferation ◽  
Mammalian Heart ◽  
Cell Cycle Reentry ◽  
And Oxidative Stress

The underlying cause of systolic heart failure is the inability of the adult mammalian heart to regenerate damaged myocardium. In contrast, some vertebrate species and immature mammals are capable of full cardiac regeneration following multiple types of injury through cardiomyocyte proliferation. Little is known about what distinguishes proliferative cardiomyocytes from terminally differentiated, nonproliferative cardiomyocytes. Recently, several reports have suggested that oxygen metabolism and oxidative stress play a pivotal role in regulating the proliferative capacity of mammalian cardiomyocytes. Moreover, reducing oxygen metabolism in the adult mammalian heart can induce cardiomyocyte cell cycle reentry through blunting oxidative damage, which is sufficient for functional improvement following myocardial infarction. Here we concisely summarize recent findings that highlight the role of oxygen metabolism and oxidative stress in cardiomyocyte cell cycle regulation, and discuss future therapeutic approaches targeting oxidative metabolism to induce cardiac regeneration.

scholarly journals Non-Coding RNAs in Breast Cancer: Intracellular and Intercellular Communication

2018 ◽  
Vol 4 (4) ◽  
pp. 40 ◽  
Author(s):  
Carolyn Klinge
Keyword(s):  
Breast Cancer ◽  
Intercellular Communication ◽  
Intracellular Signaling ◽  
Colorectal Neoplasia ◽  
Breast Tumors ◽  
Estrogen Receptor Α ◽  
Circular Rnas ◽  
Intercellular Signaling ◽  
Protein Coding ◽  
Non Coding Rnas

Non-coding RNAs (ncRNAs) are regulators of intracellular and intercellular signaling in breast cancer. ncRNAs modulate intracellular signaling to control diverse cellular processes, including levels and activity of estrogen receptor α (ERα), proliferation, invasion, migration, apoptosis, and stemness. In addition, ncRNAs can be packaged into exosomes to provide intercellular communication by the transmission of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) to cells locally or systemically. This review provides an overview of the biogenesis and roles of ncRNAs: small nucleolar RNA (snRNA), circular RNAs (circRNAs), PIWI-interacting RNAs (piRNAs), miRNAs, and lncRNAs in breast cancer. Since more is known about the miRNAs and lncRNAs that are expressed in breast tumors, their established targets as oncogenic drivers and tumor suppressors will be reviewed. The focus is on miRNAs and lncRNAs identified in breast tumors, since a number of ncRNAs identified in breast cancer cells are not dysregulated in breast tumors. The identity and putative function of selected lncRNAs increased: nuclear paraspeckle assembly transcript 1 (NEAT1), metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), steroid receptor RNA activator 1 (SRA1), colon cancer associated transcript 2 (CCAT2), colorectal neoplasia differentially expressed (CRNDE), myocardial infarction associated transcript (MIAT), and long intergenic non-protein coding RNA, Regulator of Reprogramming (LINC-ROR); and decreased levels of maternally-expressed 3 (MEG3) in breast tumors have been observed as well. miRNAs and lncRNAs are considered targets of therapeutic intervention in breast cancer, but further work is needed to bring the promise of regulating their activities to clinical use.

scholarly journals The effective function of circular RNA in colorectal cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Mandana Ameli-Mojarad ◽  
Melika Ameli-Mojarad ◽  
Mahrooyeh Hadizadeh ◽  
Chris Young ◽  
Hosna Babini ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Circular Rna ◽  
Circular Rnas ◽  
Colorectal Tumorigenesis ◽  
Non Coding Rnas ◽  
Mirna Sponges ◽  
Mechanisms Of Development

AbstractColorectal cancer (CRC) is the 3rd most common type of cancer worldwide. Late detection plays role in one-third of annual mortality due to CRC. Therefore, it is essential to find a precise and optimal diagnostic and prognostic biomarker for the identification and treatment of colorectal tumorigenesis. Covalently closed, circular RNAs (circRNAs) are a class of non-coding RNAs, which can have the same function as microRNA (miRNA) sponges, as regulators of splicing and transcription, and as interactors with RNA-binding proteins (RBPs). Therefore, circRNAs have been investigated as specific targets for diagnostic and prognostic detection of CRC. These non-coding RNAs are also linked to metastasis, proliferation, differentiation, migration, angiogenesis, apoptosis, and drug resistance, illustrating the importance of understanding their involvement in the molecular mechanisms of development and progression of CRC. In this review, we present a detailed summary of recent findings relating to the dysregulation of circRNAs and their potential role in CRC.

Abstract 20492: Mlf1 Regulates Myocyte Proliferation in Postnatal Hearts

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Shalini Muralidhar ◽  
Feng Xiao ◽  
Suwannee Thet ◽  
Hesham Sadek
Keyword(s):  
Cell Cycle ◽  
Transcription Factors ◽  
Cell Cycle Arrest ◽  
Molecular Mechanisms ◽  
Gene Array ◽  
Bhlh Transcription Factor ◽  
Cardiomyocyte Proliferation ◽  
Regenerative Capacity ◽  
Cycle Arrest ◽  
Endogenous Expression

Lower vertebrates, such as newt and zebrafish, retain a robust cardiac regenerative capacity following injury. Although adult mammals lack this cardiac regenerative potential, there is ample interest in understanding how heart regeneration occurs, and to reawaken this process in adult humans. Recently, we showed that mice are capable of regenerating their hearts shortly after birth following injury. This regenerative response is associated with robust proliferation of cardiomyocytes without significant hypertrophy or fibrosis. However, this regenerative capacity is lost by 7 days postnatally, coinciding with cell cycle arrest. In an effort to determine the mechanism of cardiomyocytes cell cycle arrest after the first week of life, we performed a gene array after cardiac injury at multiple post-natal time points. This enabled us to identify a number of transcription factors that are differentially expressed during this postnatal window. We recently reported that one of these transcription factors Meis1 regulates postnatal cell cycle arrest of cardiomyocytes. Furthermore, Myeloid leukemia factor 1 (Mlf1), a bhlh transcription factor that has not been previously studied in the heart has similar dysregulated pattern following injury. Our preliminary data with in-vitro knockdown of Mlf1 in cardiomyocyte resulted in 2-fold increase in cardiomyocyte proliferation. Furthermore, immunohistochemistry results indicated that the endogenous expression and nuclear localization of Mlf1 in the post-natal cardiomyocytes coincides with cell cycle arrest. To explore this pattern, we generated a cardiomyocyte-specific Mlf1 knockout mouse, and showed that loss of Mlf1 results in robust cardiomyocyte proliferation in postnatal hearts (P14). Additionally, we confirmed previous reports that Mlf1 regulates p53 and induces cell cycle arrest by induction of CDK inhibitors like p21 and p57 in these Mlf1 KO mice. This suggests a role of Mlf1 in promoting reactivation of injured myocardium through induction of cardiomyocyte proliferation. These findings will further provide evidences of molecular mechanisms involved in the dormant regenerative capacity in adult mammals that can be a potential target of therapeutic approaches.

scholarly journals The Impact of Mutant p53 in the Non-Coding RNA World

Biomolecules ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 472
Author(s):  
Silvia Di Agostino
Keyword(s):  
Tumor Suppressor ◽  
Human Cancer ◽  
Rna World ◽  
Circular Rnas ◽  
Mutant P53 ◽  
Suppressor Activity ◽  
Protein Coding ◽  
Micro Rnas ◽  
Non Coding Rnas ◽  
The Impact

Long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), micro RNAs (miRNAs), and extracellular RNAs (exRNAs) are new groups of RNAs with regulation activities that have low or no protein-coding ability. Emerging evidence suggests that deregulated expression of these non-coding RNAs is associated with the induction and progression of diverse tumors throughout epigenetic, transcriptional, and post-transcriptional modifications. A consistent number of non-coding RNAs (ncRNAs) has been shown to be regulated by p53, the most important tumor suppressor of the cells frequently mutated in human cancer. It has been shown that some mutant p53 proteins are associated with the loss of tumor suppressor activity and the acquisition of new oncogenic functions named gain-of-function activities. In this review, we highlight recent lines of evidence suggesting that mutant p53 is involved in the expression of specific ncRNAs to gain oncogenic functions through the creation of a complex network of pathways that influence each other.

scholarly journals Long-Noncoding RNA (lncRNA) in the Regulation of Hypoxia-Inducible Factor (HIF) in Cancer

2020 ◽  
Vol 6 (3) ◽  
pp. 27 ◽  
Author(s):  
Dominik A. Barth ◽  
Felix Prinz ◽  
Julia Teppan ◽  
Katharina Jonas ◽  
Christiane Klec ◽  
...  
Keyword(s):  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Hypoxia Inducible Factor ◽  
Protein Coding ◽  
Rna Molecules ◽  
Von Hippel Lindau ◽  
Hypoxic Conditions ◽  
Main Regulator ◽  
Upstream Regulators

Hypoxia is dangerous for oxygen-dependent cells, therefore, physiological adaption to cellular hypoxic conditions is essential. The transcription factor hypoxia-inducible factor (HIF) is the main regulator of hypoxic metabolic adaption reducing oxygen consumption and is regulated by gradual von Hippel-Lindau (VHL)-dependent proteasomal degradation. Beyond physiology, hypoxia is frequently encountered within solid tumors and first drugs are in clinical trials to tackle this pathway in cancer. Besides hypoxia, cancer cells may promote HIF expression under normoxic conditions by altering various upstream regulators, cumulating in HIF upregulation and enhanced glycolysis and angiogenesis, altogether promoting tumor proliferation and progression. Therefore, understanding the underlying molecular mechanisms is crucial to discover potential future therapeutic targets to evolve cancer therapy. Long non-coding RNAs (lncRNA) are a class of non-protein coding RNA molecules with a length of over 200 nucleotides. They participate in cancer development and progression and might act as either oncogenic or tumor suppressive factors. Additionally, a growing body of evidence supports the role of lncRNAs in the hypoxic and normoxic regulation of HIF and its subunits HIF-1α and HIF-2α in cancer. This review provides a comprehensive update and overview of lncRNAs as regulators of HIFs expression and activation and discusses and highlights potential involved pathways.

scholarly journals Mechanistic basis of neonatal heart regeneration revealed by transcriptome and histone modification profiling

2019 ◽  
Vol 116 (37) ◽  
pp. 18455-18465 ◽  
Author(s):  
Zhaoning Wang ◽  
Miao Cui ◽  
Akansha M. Shah ◽  
Wenduo Ye ◽  
Wei Tan ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Rna Binding ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Cardiac Regeneration ◽  
Later Life ◽  
Heart Regeneration ◽  
Cardiomyocyte Proliferation ◽  
Neonatal Heart ◽  
Short Period

The adult mammalian heart has limited capacity for regeneration following injury, whereas the neonatal heart can readily regenerate within a short period after birth. To uncover the molecular mechanisms underlying neonatal heart regeneration, we compared the transcriptomes and epigenomes of regenerative and nonregenerative mouse hearts over a 7-d time period following myocardial infarction injury. By integrating gene expression profiles with histone marks associated with active or repressed chromatin, we identified transcriptional programs underlying neonatal heart regeneration, and the blockade to regeneration in later life. Our results reveal a unique immune response in regenerative hearts and a retained embryonic cardiogenic gene program that is active during neonatal heart regeneration. Among the unique immune factors and embryonic genes associated with cardiac regeneration, we identified Ccl24, which encodes a cytokine, and Igf2bp3, which encodes an RNA-binding protein, as previously unrecognized regulators of cardiomyocyte proliferation. Our data provide insights into the molecular basis of neonatal heart regeneration and identify genes that can be modulated to promote heart regeneration.

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