ARID1 proteins: from transcriptional and post-translational regulation to carcinogenesis and potential therapeutics

Epigenomics ◽  
2021 ◽  
Author(s):  
Olena Odnokoz ◽  
Cindy Wavelet-Vermuse ◽  
Shelby L Hophan ◽  
Serdar Bulun ◽  
Yong Wan
Keyword(s):  
Chromatin Remodeling ◽  
Translational Regulation ◽  
Current Knowledge ◽  
Human Cancer ◽  
Regulatory Mechanisms ◽  
Cell Functions ◽  
Human Cancers ◽  
Low Levels ◽  
Potential Therapeutics

The ARID1 proteins are mutually exclusive subunits of the BRG1/BRM-associated factor (BAF) complexes that play an important role in chromatin remodeling and regulate many fundamental cell functions. The role of ARID1s is well defined as a tumor-suppressive. The cancer cells evolve different mechanisms to downregulate ARID1s and inactivate their functions. ARID1s are frequently mutated in human cancer. The recent findings of ARID1A/B downregulation at transcriptional and translational levels along with their low levels in human cancers indicate the significance of regulatory mechanisms of ARID1s in cancers. In this review, we present the current knowledge on the regulation and alterations of ARID1 protein expression in human cancers and indicate the importance of regulators of ARID1s as a prognostic marker and in potential therapeutic strategies.

scholarly journals Regulation of Rho GTPases by RhoGDIs in Human Cancers

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 1037 ◽  
Author(s):  
Cho ◽  
Kim ◽  
Baek ◽  
Kim ◽  
Lee
Keyword(s):  
Cell Migration ◽  
Cancer Progression ◽  
Anticancer Agents ◽  
Rho Gtpases ◽  
Rho Gtpase ◽  
Regulatory Mechanisms ◽  
Malignant Phenotype ◽  
Cellular Processes ◽  
Human Cancers

Rho GDP dissociation inhibitors (RhoGDIs) play important roles in various cellular processes, including cell migration, adhesion, and proliferation, by regulating the functions of the Rho GTPase family. Dissociation of Rho GTPases from RhoGDIs is necessary for their spatiotemporal activation and is dynamically regulated by several mechanisms, such as phosphorylation, sumoylation, and protein interaction. The expression of RhoGDIs has changed in many human cancers and become associated with the malignant phenotype, including migration, invasion, metastasis, and resistance to anticancer agents. Here, we review how RhoGDIs control the function of Rho GTPases by regulating their spatiotemporal activity and describe the regulatory mechanisms of the dissociation of Rho GTPases from RhoGDIs. We also discuss the role of RhoGDIs in cancer progression and their potential uses for therapeutic intervention.

scholarly journals The complex functions of microRNA-150 in allergy, autoimmunity and immune tolerance

2021 ◽  
Vol 5 (4) ◽  
pp. 195-221
Author(s):  
Katarzyna Nazimek ◽  
Keyword(s):  
Immune Responses ◽  
Immune Tolerance ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Signaling Cascades ◽  
Cell Functions ◽  
Regulatory Circuits ◽  
Complex Functions ◽  
Genetic Level

<abstract> <p>At present, special efforts are being made to develop the strategies allowing for activation of long-lasting antigen-specific immune tolerance in therapy of allergic and autoimmune diseases. Some of these therapeutic approaches are aimed at modulating cell functions at genetic level by using miRNA-based and miRNA-targeting treatments. Simultaneously, the crucial role of extracellular vesicles as natural miRNA conveyors is highlighted for induction of antigen-specific immune tolerance, especially that they appear to be easily manipulatable for therapeutic applications. Among other immune-related miRNAs, miR-150 is getting special attention as it is differently expressed by immune cells at various stages of their maturation and differentiation. In addition, miR-150 is involved in different signaling cascades orchestrating humoral and cell-mediated mechanisms of both innate and adaptive immune responses. Therefore, miR-150 is considered a master regulator of immunity in mammals. Currently, physiological miR-150-dependent regulatory circuits and causes of their malfunctioning that underlie the pathogenesis of allergic and autoimmune disorders are being unraveled. Thus, present review summarizes the current knowledge of the role of miR-150 in the pathogenesis and complications of these diseases. Furthermore, the involvement of miR-150 in regulation of immune responses to allergens and self-antigens and in induction of antigen-specific immune tolerance is discussed with the special emphasis on the therapeutic potential of this miRNA.</p> </abstract>

scholarly journals Regulation of ST6GAL1 sialyltransferase expression in cancer cells

Glycobiology ◽  
2020 ◽  
Author(s):  
Kaitlyn A Dorsett ◽  
Michael P Marciel ◽  
Jihye Hwang ◽  
Katherine E Ankenbauer ◽  
Nikita Bhalerao ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Translational Regulation ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Sialic Acids ◽  
Invasion Resistance ◽  
Cell Behaviors ◽  
Molecular Events ◽  
Wide Range

Abstract The ST6GAL1 sialyltransferase, which adds α2–6 linked sialic acids to N-glycosylated proteins, is overexpressed in a wide range of human malignancies. Recent studies have established the importance of ST6GAL1 in promoting tumor cell behaviors such as invasion, resistance to cell stress, and chemoresistance. Furthermore, ST6GAL1 activity has been implicated in imparting cancer stem cell characteristics. However, despite the burgeoning interest in the role of ST6GAL1 in the phenotypic features of tumor cells, insufficient attention has been paid to the molecular mechanisms responsible for ST6GAL1 upregulation during neoplastic transformation. Evidence suggests that these mechanisms are multifactorial, encompassing genetic, epigenetic, transcriptional, and post-translational regulation. The purpose of this review is to summarize current knowledge regarding the molecular events that drive enriched ST6GAL1 expression in cancer cells.

scholarly journals CDK12: A Potent Target and Biomarker for Human Cancer Therapy

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1483 ◽  
Author(s):  
Shujing Liang ◽  
Lifang Hu ◽  
Zixiang Wu ◽  
Zhihao Chen ◽  
Shuyu Liu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cancer Therapy ◽  
Gene Transcription ◽  
Rna Splicing ◽  
Cell Cycle Progression ◽  
Current Knowledge ◽  
Human Cancer ◽  
Cellular Processes ◽  
Potential Target ◽  
Human Cancers

Cyclin-dependent kinases (CDKs) are a group of serine/threonine protein kinases and play crucial roles in various cellular processes by regulating cell cycle and gene transcription. Cyclin-dependent kinase 12 (CDK12) is an important transcription-associated CDK. It shows versatile roles in regulating gene transcription, RNA splicing, translation, DNA damage response (DDR), cell cycle progression and cell proliferation. Recently, increasing evidence demonstrates the important role of CDK12 in various human cancers, illustrating it as both a biomarker of cancer and a potential target for cancer therapy. Here, we summarize the current knowledge of CDK12, and review the research advances of CDK12′s biological functions, especially its role in human cancers and as a potential target and biomarker for cancer therapy.

scholarly journals Homeobox genes and Hepatocellular Carcinoma

2019 ◽  
Author(s):  
Kwei-Yan Liu ◽  
Li-Ting Wang ◽  
Shih-Hsien Hsu ◽  
Shen-Nien Wang
Keyword(s):  
Hepatocellular Carcinoma ◽  
Hox Genes ◽  
Viral Infections ◽  
Human Cancer ◽  
Control Cell ◽  
Environmental Toxins ◽  
Regulatory Mechanisms ◽  
Transcription Factor Family ◽  
Potential Use

Hepatocellular carcinoma (HCC) is the fifth most common type of cancer, and is the third leading cause of cancer-related deaths each year. It involves a multi-step progression and is strongly associated with chronic inflammation induced by the intake of environmental toxins and/or viral infections (i.e., hepatitis B and C viruses). Although several genetic dysregulations are considered to be involved in disease progression, the detailed regulatory mechanisms are not well defined. Homeobox (Hox) genes that encode transcription factors with homeodomains control cell growth, differentiation, and morphogenesis in embryonic development. Recently, more aberrant expressions of Hox genes were found in a wide variety of human cancer, including HCC. In this review, we summarize the currently available evidence related to the role of Hox genes in the development of HCC. The objective is to determine the roles of this conserved transcription factor family and its potential use as a therapeutic target in future investigations.

scholarly journals The Regulatory Role of RNA Metabolism Regulator TDP-43 in Human Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Xueyou Ma ◽  
Yufan Ying ◽  
Haiyun Xie ◽  
Xiaoyan Liu ◽  
Xiao Wang ◽  
...  
Keyword(s):  
Dna Binding ◽  
Human Cancer ◽  
Target Therapy ◽  
Dna Binding Protein ◽  
Rna Metabolism ◽  
Basic Knowledge ◽  
Tumor Target ◽  
Human Cancers ◽  
Rna And Dna

TAR-DNA-binding protein-43 (TDP-43) is a member of hnRNP family and acts as both RNA and DNA binding regulator, mediating RNA metabolism and transcription regulation in various diseases. Currently, emerging evidence gradually elucidates the crucial role of TDP-43 in human cancers like it is previously widely researched in neurodegeneration diseases. A series of RNA metabolism events, including mRNA alternative splicing, transport, stability, miRNA processing, and ncRNA regulation, are all confirmed to be closely involved in various carcinogenesis and tumor progressions, which are all partially regulated and interacted by TDP-43. Herein we conducted the first overall review about TDP-43 and cancers to systematically summarize the function and precise mechanism of TDP-43 in different human cancers. We hope it would provide basic knowledge and concepts for tumor target therapy and biomarker diagnosis in the future.

scholarly journals The Role of BRG1 in Antioxidant and Redox Signaling

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Shilong You ◽  
Ying Zhang ◽  
Jiaqi Xu ◽  
Hao Qian ◽  
Shaojun Wu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Chromatin Remodeling ◽  
Redox Homeostasis ◽  
Redox Signaling ◽  
Normal Functioning ◽  
Antioxidant Genes ◽  
Cellular Processes ◽  
Cell Functions ◽  
Chromatin Remodeling Complex

Redox homeostasis is regulated by critical molecules that modulate antioxidant and redox signaling (ARS) within the cell. Imbalances among these molecules can lead to oxidative stress and damage to cell functions, causing a variety of diseases. Brahma-related gene 1 (BRG1), also known as SMARCA4, is the central ATPase catalytic subunit of the switch/sucrose nonfermentable (SWI/SNF) chromatin remodeling complex, which plays a core role in DNA replication, repair, recombination, and transcriptional regulation. Numerous recent studies show that BRG1 is involved in the regulation of various cellular processes associated with ARS. BRG1, as a major factor in chromatin remodeling, is essential for the repair of oxidative stress-induced DNA damage and the activation of antioxidant genes under oxidative stress. Consequently, a comprehensive understanding of the roles of BRG1 in redox homeostasis is crucial to understand the normal functioning as well as pathological mechanisms. In this review, we summarized and discussed the role of BRG1 in the regulation of ARS.

scholarly journals When and How Do Emotional Intelligence and Flourishing Protect against Suicide Risk in Adolescent Bullying Victims?

2019 ◽  
Vol 16 (12) ◽  
pp. 2114 ◽  
Author(s):  
Lourdes Rey ◽  
Sergio Mérida-López ◽  
Nicolás Sánchez-Álvarez ◽  
Natalio Extremera
Keyword(s):  
Emotional Intelligence ◽  
Suicide Risk ◽  
Current Knowledge ◽  
Protective Role ◽  
Proposed Model ◽  
Mediator Role ◽  
Low Levels ◽  
Bullying Victims ◽  
The Relationship

This study contributes to current knowledge on the protective role of emotional intelligence and flourishing in cases of suicide risk (namely depressive symptoms and suicidal ideation) in a sample of adolescent victims of traditional bullying. The proposed model tested the mediator role of flourishing in the relationship between emotional intelligence (EI) and suicide risk together with the moderating effect of EI in the relationship between low flourishing and increased suicide risk. Considering an initial sample of 1847 adolescents (52.5% female), a subsample of 494 pure bullying victims (61.3% female) took part in this research. The main results showed EI to be linked to decreased suicide risk through levels of flourishing. Moreover, EI buffered the relationship between low flourishing and the associated suicide risk. Victimized adolescents with both low levels of EI and of flourishing reported higher levels of suicide risk than their counterparts with high EI levels. This suggests the protective role of EI of both predicting higher flourishing and reducing the likelihood of suicide risk among victimized adolescents with low levels of flourishing. Finally, the practical implications of these novel findings regarding the role of EI and flourishing in the prevention of suicide risk among victimized adolescents are discussed.

scholarly journals MicroRNAs as Important Players and Biomarkers in Oral Carcinogenesis

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Anjie Min ◽  
Chao Zhu ◽  
Shuping Peng ◽  
Saroj Rajthala ◽  
Daniela Elena Costea ◽  
...  
Keyword(s):  
Low Income ◽  
Noncoding Rna ◽  
Current Knowledge ◽  
Human Cancer ◽  
Low Income Countries ◽  
Rna Molecules ◽  
Therapeutic Modalities ◽  
Oral Carcinogenesis ◽  
Significant Attention

Oral cancer, represented mainly by oral squamous cell carcinoma (OSCC), is the eighth most common type of human cancer worldwide. The number of new OSCC cases is increasing worldwide, especially in the low-income countries, and the prognosis remains poor in spite of recent advances in the diagnostic and therapeutic modalities. MicroRNAs (miRNAs), 18–25 nucleotides long noncoding RNA molecules, have recently gained significant attention as potential regulators and biomarkers for carcinogenesis. Recent data show that several miRNAs are deregulated in OSCC, and they have either a tumor suppressive or an oncogenic role in oral carcinogenesis. This review summarizes current knowledge on the role of miRNAs as tumor promotors or tumor suppressors in OSCC development and discusses their potential value as diagnostic and prognostic markers in OSCC.

scholarly journals Complement System: Promoter or Suppressor of Cancer Progression?

Antibodies ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 57
Author(s):  
Margot Revel ◽  
Marie V. Daugan ◽  
Catherine Sautés-Fridman ◽  
Wolf H. Fridman ◽  
Lubka T. Roumenina
Keyword(s):  
Cancer Progression ◽  
Complement System ◽  
Current Knowledge ◽  
Prognostic Impact ◽  
Cancer Type ◽  
Human Cancers ◽  
Cancer Types ◽  
The Complement System

Constituent of innate immunity, complement is present in the tumor microenvironment. The functions of complement include clearance of pathogens and maintenance of homeostasis, and as such could contribute to an anti-tumoral role in the context of certain cancers. However, multiple lines of evidence show that in many cancers, complement has pro-tumoral actions. The large number of complement molecules (over 30), the diversity of their functions (related or not to the complement cascade), and the variety of cancer types make the complement-cancer topic a very complex matter that has just started to be unraveled. With this review we highlight the context-dependent role of complement in cancer. Recent studies revealed that depending of the cancer type, complement can be pro or anti-tumoral and, even for the same type of cancer, different models presented opposite effects. We aim to clarify the current knowledge of the role of complement in human cancers and the insights from mouse models. Using our classification of human cancers based on the prognostic impact of the overexpression of complement genes, we emphasize the strong potential for therapeutic targeting the complement system in selected subgroups of cancer patients.

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