Potential therapeutic strategies for targeting Y-box-binding protein 1 in cancers

2021 ◽  
Vol 21 ◽  
Author(s):  
Jia-Wei Yang ◽  
Chao Sun ◽  
Qiu-Yang Jin ◽  
Xing-Hui Qiao ◽  
Xiu-Li Guo
Keyword(s):  
Nuclear Translocation ◽  
Binding Protein ◽  
Circular Rna ◽  
Therapeutic Strategies ◽  
Mrna Splicing ◽  
Tumor Proliferation ◽  
Normal Cells ◽  
The Past ◽  
Potential Cancer

: As one of the most conservative proteins in evolution, Y-box-binding protein 1 (YB-1) has long been considered as a potential cancer target. YB-1 is usually poorly expressed in normal cells and exerts cellular physiological functions such as DNA repair, pre-mRNA splicing and mRNA stabilizing. In cancer cells, the expression of YB-1 is up-regulated and undergoes nuclear translocation and contributes to tumorigenesis, angiogenesis, tumor proliferation, invasion, migration and chemotherapy drug resistance. During the past decades, a variety of pharmacological tools such as siRNA, shRNA, microRNA, circular RNA, lncRNA and various compounds have been developed to target YB-1 for cancer therapy. In this review, we describe the physiological characteristics of YB-1 in detail, highlight the role of YB-1 in tumors and summarize the current therapeutic methods for targeting YB-1 in cancer.

scholarly journals Delta-secretase (AEP) mediates tau-splicing imbalance and accelerates cognitive decline in tauopathies

2018 ◽  
Vol 215 (12) ◽  
pp. 3038-3056 ◽  
Author(s):  
Zhi-Hao Wang ◽  
Pai Liu ◽  
Xia Liu ◽  
Shan Ping Yu ◽  
Jian-Zhi Wang ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Kinase Activity ◽  
Nuclear Translocation ◽  
Memory Deficits ◽  
Mrna Splicing ◽  
Splicing Factors ◽  
Synaptic Functions ◽  
Tau Isoforms ◽  
Exon 10

SRPK2 is abnormally activated in tauopathies including Alzheimer’s disease (AD). SRPK2 is known to play an important role in pre–mRNA splicing by phosphorylating SR-splicing factors. Dysregulation of tau exon 10 pre–mRNA splicing causes pathological imbalances in 3R- and 4R-tau, leading to neurodegeneration; however, the role of SRPK2 in these processes remains unclear. Here we show that delta-secretase (also known as asparagine endopeptidase; AEP), which is activated in AD, cleaves SRPK2 and increases its nuclear translocation as well as kinase activity, augmenting exon 10 inclusion. Conversely, AEP-uncleavable SRPK2 N342A mutant increases exon 10 exclusion. Lentiviral expression of truncated SRPK2 increases 4R-tau isoforms and accelerates cognitive decline in htau mice. Uncleavable SRPK2 N342A expression improves synaptic functions and prevents spatial memory deficits in tau intronic mutant FTDP-17 transgenic mice. Hence, AEP mediates tau-splicing imbalance in tauopathies via cleaving SRPK2.

Basic Overview of Current Immunotherapy Approaches in Cancer

2016 ◽  
pp. 298-308 ◽  
Author(s):  
Vamsidhar Velcheti ◽  
Kurt Schalper
Keyword(s):  
Immune Evasion ◽  
Immune Checkpoint ◽  
Immune Checkpoint Blockade ◽  
Therapeutic Strategies ◽  
Checkpoint Blockade ◽  
Basic Principles ◽  
The Past ◽  
Recent Success

Recent success of immunotherapy strategies such as immune checkpoint blockade in several malignancies has established the role of immunotherapy in the treatment of cancer. Cancers use multiple mechanisms to co-opt the host-tumor immune interactions, leading to immune evasion. Our understanding of the host-tumor interactions has evolved over the past few years and led to various promising new therapeutic strategies. This article will focus on the basic principles of immunotherapy, novel pathways/agents, and combinatorial immunotherapies.

scholarly journals Mining the Gut Microbiota for Microbial-Based Therapeutic Strategies in Cancer Immunotherapy

2021 ◽  
Vol 11 ◽  
Author(s):  
Bolei Li ◽  
Tao Gong ◽  
Yu Hao ◽  
Xuedong Zhou ◽  
Lei Cheng
Keyword(s):  
Immune System ◽  
Gut Microbiota ◽  
Cancer Immunotherapy ◽  
Critical Role ◽  
Therapeutic Strategies ◽  
Host Immune System ◽  
The Past ◽  
Promising Strategy

The past two decades witnessed a revolution in our understanding of host–microbiota interactions that led to the concept of the super-organism consisting of a eukaryotic part and a prokaryotic part. Owing to the critical role of gut microbiota in modulating the host immune system, it is not beyond all expectations that more and more evidence indicated that the shift of gut microbiota influenced responses to numerous forms of cancer immunotherapy. Therapy targeting gut microbiota is becoming a promising strategy to improve cancer immunotherapy. In this review, we discuss the role of the gut microbiota in response to cancer immunotherapy, the mechanisms that the gut microbiota influences cancer immunotherapy, and therapeutic strategies targeting gut microbiota to improve cancer immunotherapy.

scholarly journals Intracellular Ca2 + Imbalance Critically Contributes to Paraptosis

2021 ◽  
Vol 8 ◽  
Author(s):  
Eunhee Kim ◽  
Dong Min Lee ◽  
Min Ji Seo ◽  
Hong Jae Lee ◽  
Kyeong Sook Choi
Keyword(s):  
Therapeutic Strategy ◽  
Ion Homeostasis ◽  
Proteasome Inhibitors ◽  
Therapeutic Strategies ◽  
Regulatory Mechanisms ◽  
Mediated Communication ◽  
Flux System ◽  
Intracellular Ca ◽  
Potential Cancer

Paraptosis is a type of programmed cell death that is characterized by dilation of the endoplasmic reticulum (ER) and/or mitochondria. Since paraptosis is morphologically and biochemically different from apoptosis, understanding its regulatory mechanisms may provide a novel therapeutic strategy in malignant cancer cells that have proven resistant to conventional pro-apoptotic treatments. Relatively little is known about the molecular basis of paraptosis, but perturbations of cellular proteostasis and ion homeostasis appear to critically contribute to the process. Ca2+ transport has been shown to be important in the paraptosis induced by several natural products, metal complexes, and co-treatment with proteasome inhibitors and certain Ca2+-modulating agents. In particular, the Ca2+-mediated communication between the ER and mitochondria plays a crucial role in paraptosis. Mitochondrial Ca2+ overload from the intracellular Ca2+-flux system located at the ER–mitochondrial axis can induce mitochondrial dilation during paraptosis, while the accumulation of misfolded proteins within the ER lumen is believed to exert an osmotic force and draw water from the cytoplasm to distend the ER lumen. In this process, Ca2+ release from the ER also critically contributes to aggravating ER stress and ER dilation. This review focuses on the role of Ca2+ transport in paraptosis by summarizing the recent findings related to the actions of Ca2+-modulating paraptosis-inducing agents and discussing the potential cancer therapeutic strategies that may effectively induce paraptosis via Ca2+ signaling.

scholarly journals The gut in iron homeostasis: role of HIF-2 under normal and pathological conditions

Blood ◽  
2013 ◽  
Vol 122 (6) ◽  
pp. 885-892 ◽  
Author(s):  
Maria Mastrogiannaki ◽  
Pavle Matak ◽  
Carole Peyssonnaux
Keyword(s):  
Iron Homeostasis ◽  
Molecular Mechanisms ◽  
Iron Absorption ◽  
Hypoxia Inducible Factor ◽  
Therapeutic Strategies ◽  
The Past ◽  
Pathological Conditions ◽  
Per Se ◽  
Key Genes

Abstract Although earlier, seminal studies demonstrated that the gut per se has the intrinsic ability to regulate the rates of iron absorption, the spotlight in the past decade has been placed on the systemic regulation of iron homeostasis by the hepatic hormone hepcidin and the molecular mechanisms that regulate its expression. Recently, however, attention has returned to the gut based on the finding that hypoxia inducible factor-2 (HIF-2α) regulates the expression of key genes that contribute to iron absorption. Here we review the current understanding of the molecular mechanisms that regulate iron homeostasis in the gut by focusing on the role of HIF-2 under physiological steady-state conditions and in the pathogenesis of iron-related diseases. We also discuss implications for adapting HIF-2–based therapeutic strategies in iron-related pathological conditions.

scholarly journals Corrigendum: A Role of U12 Intron in Proper Pre-mRNA Splicing of Plant Cap Binding Protein 20 Genes

2019 ◽  
Vol 10 ◽  
Author(s):  
Marcin Pieczynski ◽  
Katarzyna Kruszka ◽  
Dawid Bielewicz ◽  
Jakub Dolata ◽  
Michal Szczesniak ◽  
...  
Keyword(s):  
Binding Protein ◽  
Mrna Splicing

scholarly journals Microbial biofilm: a “sticky” problem

2018 ◽  
Vol 33 (1) ◽  
Author(s):  
Arianna Pompilio ◽  
Giovanni Di Bonaventura
Keyword(s):  
Biofilm Formation ◽  
Therapeutic Strategies ◽  
Review Article ◽  
Bacterial Biofilm ◽  
Formation Mechanisms ◽  
The Past ◽  
Underlying Mechanisms ◽  
Biofilm Development ◽  
Multispecies Biofilms

Bacteria can form, on virtually any surface, single- and multispecies biofilms intrinsically resistant/tolerant to antibiotics and elusive of the host immune response. The study of bacterial biofilm development has, therefore, received great interest over the past 20 years and is motivated by the well-recognized role of these multicellular communities in infectious diseases. In this review article, we provide a synopsis of (i) biofilm formation mechanisms; (ii) biofilm clinical significance and underlying mechanisms; (iii) the current methodologies for microbiological diagnosis of biofilm-related infections; and (iv) current and future therapeutic strategies to combat biofilm-associated infections.

scholarly journals Cholesterol and Sphingolipid Enriched Lipid Rafts as Therapeutic Targets in Cancer

2021 ◽  
Vol 22 (2) ◽  
pp. 726
Author(s):  
Michela Codini ◽  
Mercedes Garcia-Gil ◽  
Elisabetta Albi
Keyword(s):  
Lipid Rafts ◽  
Cholesterol Content ◽  
Membrane Lipid ◽  
Therapeutic Strategies ◽  
Membrane Properties ◽  
Cellular Processes ◽  
The Past ◽  
Nuclear Membranes ◽  
Technical Advances

Lipid rafts are critical cell membrane lipid platforms enriched in sphingolipid and cholesterol content involved in diverse cellular processes. They have been proposed to influence membrane properties and to accommodate receptors within themselves by facilitating their interaction with ligands. Over the past decade, technical advances have improved our understanding of lipid rafts as bioactive structures. In this review, we will cover the more recent findings about cholesterol, sphingolipids and lipid rafts located in cellular and nuclear membranes in cancer. Collectively, the data provide insights on the role of lipid rafts as biomolecular targets in cancer with good perspectives for the development of innovative therapeutic strategies.

Deletion of the mouse GH-binding protein (mGHBP) mRNA polyadenylation and splicing sites does not abolish production of mGHBP

1997 ◽  
Vol 19 (1) ◽  
pp. 1-13 ◽  
Author(s):  
Y Zhou ◽  
L He ◽  
G Baumann ◽  
J J Kopchick
Keyword(s):  
Genomic Sequence ◽  
Binding Protein ◽  
Mrna Splicing ◽  
Splice Acceptor Site ◽  
Acceptor Site ◽  
Carboxy Terminus ◽  
Regulation Of Expression ◽  
Gh Receptor ◽  
Selection Of

ABSTRACT In murine species, the GH receptor (mGHR) gene encodes a full-length membrane-anchored mGHR and a truncated soluble receptor ectodomain (the GH-binding protein; mGHBP). The mGHR and mGHBP mRNAs are generated by alternative pre-mRNA splicing. Similar GHR/GHBP pairs are generated in other species by proteolysis of the GHR. The regulation of GHBP expression and the biological role of GHBP are not clear. In order to begin to dissect the factors responsible for regulating expression of mGHR and mGHBP, we have cloned a mouse GH receptor/binding protein (mGHR/BP) minigene consisting of two mGHR cDNA fragments and an mGHR/BP genomic sequence, such that the mGHR and mGHBP can be derived from the minigene by mimicking native alternative pre-mRNA splicing. To study the possible role of selection of polyadenylation relative to the expression of mGHR and mGHBP, we deleted the two tandem poly A addition signals and the flanking AT-rich region within the exon (exon 8A) that encodes the carboxy terminus of mGHBP. In addition, two other mutated forms of the minigene, one containing a mutated alternative splice acceptor site (SAS) near exon 8A and the other possessing a deletion of the intron between exons 7 and 8A (intron 7/8A), were generated. Expression of the mGHR/BP minigene and its mutated forms in transfected mouse L cells revealed that removal of the polyadenylation signals diminished but did not abolish either mGHR or mGHBP production. However, mutation of the SAS yielded normal mGHR and an mGHBP which may be a result of the translation of an mRNA possessing an open reading frame in intron 7/8A. Additionally, removal of intron 7/8A abolished mGHR expression but resulted in mGHBP production. The results suggest that selection of alternative polyadenylation sites of the mGHR/BP gene does not play a major role in the regulation of expression of mGHR and mGHBP in vitro. These results also suggest that mutation of the SAS near exon 8A does not abolish the ability of mGHR/BP gene to produce an mGHBP that retains the ability to bind GH, although the new mGHBP may be different from the natural mGHBP at its carboxy terminus.

scholarly journals Circular RNAs in the Regulation of Oxidative Stress

2021 ◽  
Vol 12 ◽  
Author(s):  
Yao Zhang ◽  
Yu Chen ◽  
Yue Wan ◽  
Yueshui Zhao ◽  
Qinglian Wen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Free Radicals ◽  
Science And Technology ◽  
Circular Rna ◽  
Reactive Metabolites ◽  
Circular Rnas ◽  
Stress System ◽  
The Past ◽  
The Relationship

Oxidative stress caused by an imbalance between the production and elimination of reactive metabolites and free radicals can lead to the development of a variety of diseases. Over the past years, with the development of science and technology, circular RNA (circRNA) has been found to be closely associated with oxidative stress, which plays an important role in the process of oxidative stress. Currently, the understanding of circRNAs in the mechanism of oxidative stress is limited. In this review, we described the relationship between oxidative stress and circRNAs, the circRNAs related to oxidative stress, and the role of circRNAs in promoting or inhibiting the occurrence and development of diseases associated with the oxidative stress system.

Sign in / Sign up

Export Citation Format

Share Document