Interaction of ncRNA and Epigenetic Modifications in Gastric Cancer: Focus on Histone Modification DOI Creative Commons
Qingfan Yang, Yu Chen, Rui Guo

et al.

Frontiers in Oncology, Journal Year: 2022, Volume and Issue: 11

Published: Jan. 26, 2022

Gastric cancer has developed as a very common gastrointestinal tumors, with recent effective advancements in the diagnosis and treatment of early gastric cancer. However, prognosis for remains poor. As result, there is sore need better understanding mechanisms development progression to improve existing diagnostic options. In years, epigenetics been recognized an important contributor on tumor progression. Epigenetic changes include chromatin remodeling, DNA methylation histone modifications. An increasing number studies demonstrated that noncoding RNAs (ncRNAs) are associated epigenetic Herein, we describe molecular interactions modifications ncRNAs epigenetics. We focus ncRNA-mediated gene expression tumorigenesis This mechanism will contribute our deeper carcinogenesis progression, thus providing innovations strategies.

Language: Английский

Lipogenesis inhibitors: therapeutic opportunities and challenges DOI Creative Commons
Battsetseg Batchuluun,

Stephen L. Pinkosky,

Gregory R. Steinberg

et al.

Nature Reviews Drug Discovery, Journal Year: 2022, Volume and Issue: 21(4), P. 283 - 305

Published: Jan. 14, 2022

Fatty acids are essential for survival, acting as bioenergetic substrates, structural components and signalling molecules. Given their vital role, cells have evolved mechanisms to generate fatty from alternative carbon sources, through a process known de novo lipogenesis (DNL). Despite the importance of DNL, aberrant upregulation is associated with wide variety pathologies. Inhibiting core enzymes including citrate/isocitrate carrier (CIC), ATP-citrate lyase (ACLY), acetyl-CoA carboxylase (ACC) acid synthase (FAS), represents an attractive therapeutic strategy. challenges related efficacy, selectivity safety, several new classes synthetic DNL inhibitors entered clinical-stage development may become foundation class therapeutics. De (DNL) maintenance whole-body cellular homeostasis, but pathway broad range conditions, cardiovascular disease, metabolic disorders cancers. Here, Steinberg colleagues provide overview physiological pathological roles assess strategies agents currently in therapeutically target them.

Language: Английский

Citations

265
CircRNA-CREIT inhibits stress granule assembly and overcomes doxorubicin resistance in TNBC by destabilizing PKR DOI Creative Commons
Xiaolong Wang, Tong Chen, Chen Li

et al.

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: Aug. 29, 2022

Circular RNAs (circRNAs) represent a novel type of regulatory RNA characterized by high evolutionary conservation and stability. CircRNAs are expected to be potential diagnostic biomarkers therapeutic targets for variety malignancies. However, the functions underlying mechanisms circRNAs in triple-negative breast cancer (TNBC) largely unknown.

Language: Английский

Citations

114
UbiBrowser 2.0: a comprehensive resource for proteome-wide known and predicted ubiquitin ligase/deubiquitinase–substrate interactions in eukaryotic species DOI
Xun Wang, Yang Li, Mengqi He

et al.

Nucleic Acids Research, Journal Year: 2021, Volume and Issue: 50(D1), P. D719 - D728

Published: Oct. 6, 2021

Abstract As an important post-translational modification, ubiquitination mediates ∼80% of protein degradation in eukaryotes. The degree is tightly determined by the delicate balance between specific ubiquitin ligase (E3)-mediated and deubiquitinase-mediated deubiquitination. In 2017, we developed UbiBrowser 1.0, which integrated database for predicted human proteome-wide E3–substrate interactions. Here, to meet urgent requirement E3/deubiquitinase–substrate interactions (ESIs/DSIs) multiple organisms, updated version 2.0 (http://ubibrowser.ncpsb.org.cn). Using improved protocol, collected 4068/967 known ESIs/DSIs manual curation, about 2.2 million highly confident 39 with >210-fold increase total data volume. addition, made several new features version: (i) it allows exploring proteins’ upstream E3 ligases deubiquitinases simultaneously; (ii) has significantly increased species coverage; (iii) presents a uniform confidence scoring system rank ESIs/DSIs. To facilitate usage 2.0, also redesigned web interface these ESIs/DSIs, added functions ‘Browse’, ‘Download’ ‘Application Programming Interface’. We believe that as discovery tool, will contribute study development drug targets complex diseases.

Language: Английский

Citations

103
Ubiquitination and deubiquitination in cancer: from mechanisms to novel therapeutic approaches DOI Creative Commons
Fangfang Liu, Jingyu Chen, Kai Li

et al.

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: July 25, 2024

Abstract Ubiquitination, a pivotal posttranslational modification of proteins, plays fundamental role in regulating protein stability. The dysregulation ubiquitinating and deubiquitinating enzymes is common feature various cancers, underscoring the imperative to investigate ubiquitin ligases deubiquitinases (DUBs) for insights into oncogenic processes development therapeutic interventions. In this review, we discuss contributions ubiquitin–proteasome system (UPS) all hallmarks cancer progress drug discovery. We delve multiple functions UPS oncology, including its regulation cancer-associated pathways, metabolic reprogramming, engagement with tumor immune responses, function phenotypic plasticity polymorphic microbiomes, other essential cellular functions. Furthermore, provide comprehensive overview novel anticancer strategies that leverage UPS, application proteolysis targeting chimeras (PROTACs) molecular glues.

Language: Английский

Citations

39
Post-Translational Modifications of Proteins Orchestrate All Hallmarks of Cancer DOI Creative Commons
Pathea Bruno,

Aneeta Arshad,

Maria-Raluca Gogu

et al.

Life, Journal Year: 2025, Volume and Issue: 15(1), P. 126 - 126

Published: Jan. 18, 2025

Post-translational modifications (PTMs) of proteins dynamically build the buffering and adapting interface between oncogenic mutations environmental stressors, on one hand, cancer cell structure, functioning, behavior. Aberrant PTMs can be considered as enabling characteristics long they orchestrate all malignant variability in proteome cells, cancer-associated tumor microenvironment (TME). On other enhance anticancer mechanisms tumoral ecosystem or sustain beneficial effects oncologic therapies through degradation inactivation carcinogenic or/and activation tumor-suppressor proteins. In this review, we summarized analyzed a wide spectrum involved regulatory that drive tumorigenesis, genetic instability, epigenetic reprogramming, events metastatic cascade, cytoskeleton extracellular matrix (ECM) remodeling, angiogenesis, immune response, tumor-associated microbiome, metabolism rewiring most important hallmarks cancer. All develop due to proteins, which modulate gene transcription, intracellular signaling, protein size, activity, stability localization, trafficking, secretion, half-life, protein–protein interactions (PPIs). associated with exploited better understand underlying molecular heterogeneous chameleonic disease, find new biomarkers progression prognosis, personalize oncotherapies, discover targets for drug development.

Language: Английский

Citations

2
Mechanisms, Diagnosis and Treatment of Bone Metastases DOI Creative Commons

Jozef Ban,

Valerie Fock,

Dave N.T. Aryee

et al.

Cells, Journal Year: 2021, Volume and Issue: 10(11), P. 2944 - 2944

Published: Oct. 29, 2021

Bone and bone marrow are among the most frequent metastatic sites of cancer. The occurrence metastasis is frequently associated with a dismal disease outcome. prevention therapy metastases priority in treatment cancer patients. However, current therapeutic options for patients limited efficacy increased morbidity. Therefore, therapies mainly palliative nature. A better understanding underlying molecular pathways process warranted to develop novel, well-tolerated more successful treatments significant improvement patients’ quality life In this review, we provide comparative mechanistic insights into various solid tumors, including pediatric cancers. We also highlight innovative approaches biologically targeted immunotherapy. particular, discuss role microenvironment attraction, homing, dormancy outgrowth tumor cells ensuing implications. Multiple signaling have been described contribute spread specific entities, knowledge derived from study breast prostate it likely that similar mechanisms involved different types cancer, multiple myeloma, primary sarcomas neuroblastoma. rate-limiting interaction cellular noncellular components bone-marrow niche provides attractive targets, which already partially exploited by novel promising immunotherapies.

Language: Английский

Citations

63
Plants as a Source of Anticancer Agents: From Bench to Bedside DOI Creative Commons
Wamidh H. Talib, Safa Daoud, Asma Ismail Mahmod

et al.

Molecules, Journal Year: 2022, Volume and Issue: 27(15), P. 4818 - 4818

Published: July 27, 2022

Cancer is the second leading cause of death after cardiovascular diseases. Conventional anticancer therapies are associated with lack selectivity and serious side effects. hallmarks biological capabilities acquired by cancer cells during neoplastic transformation. Targeting multiple a promising strategy to treat cancer. The diversity in chemical structure relatively low toxicity make plant-derived natural products source for development new more effective that have capacity target In this review, we discussed activities ten extracted from plants. majority these inhibit targeting hallmarks, many chemicals reached clinical applications. Studies review provide solid ground researchers physicians design combination using products.

Language: Английский

Citations

45
Proteomics of post-translational modifications in colorectal cancer: Discovery of new biomarkers DOI

Gengjun Zhu,

Lifang Jin, Wanchun Sun

et al.

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2022, Volume and Issue: 1877(4), P. 188735 - 188735

Published: May 13, 2022

Language: Английский

Citations

39
The Next Frontier: Translational Development of Ubiquitination, SUMOylation, and NEDDylation in Cancer DOI Open Access

Nicole E. Pellegrino,

Arcan Güven, Kayleigh Gray

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(7), P. 3480 - 3480

Published: March 23, 2022

Post-translational modifications of proteins ensure optimized cellular processes, including proteostasis, regulated signaling, cell survival, and stress adaptation to maintain a balanced homeostatic state. Abnormal post-translational are associated with dysfunction the occurrence life-threatening diseases, such as cancer neurodegenerative diseases. Therefore, some frequently seen protein have been used disease markers, while others targeted for developing specific therapies. The ubiquitin ubiquitin-like modifiers, namely, small modifier (SUMO) neuronal precursor cell-expressed developmentally down-regulated 8 (NEDD8), share several features, structures, enzymatic cascades mediating conjugation process, amino acid residues. Alterations in regulatory mechanisms lead aberrations biological processes during tumorigenesis, regulation tumor metabolism, immunological modulation microenvironment, stem stemness, besides many more. Novel insights into pathways involved biology reveal potential interplay between ubiquitination, SUMOylation, NEDDylation. This review outlines current understandings assay capabilities It will further highlight role NEDDylation tumorigenesis.

Language: Английский

Citations

38
E3 ubiquitin ligases SINA4 and SINA11 regulate anthocyanin biosynthesis by targeting the IAA29‐ARF5‐1‐ERF3 module in apple DOI

Hong‐Liang Li,

Zhiying Liu, Xiaona Wang

et al.

Plant Cell & Environment, Journal Year: 2023, Volume and Issue: 46(12), P. 3902 - 3918

Published: Sept. 1, 2023

Auxin/indole-3-acetic acid (AUX/IAA) and auxin response factor (ARF) proteins are important components of the signalling pathway, but their ubiquitination modification mechanism auxin-mediated anthocyanin biosynthesis remain elusive. Here, ARF MdARF5-1 was identified as a negative regulator in apple, it integrates ethylene signals by inhibiting expression MdERF3. The repressor MdIAA29 decreased inhibitory effect on attenuating transcriptional inhibition MdERF3 MdARF5-1. In addition, E3 ubiquitin ligases MdSINA4 MdSINA11 played positive regulatory roles targeting for degradation, respectively. destabilized to regulate accumulation signalling. sum, our data revealed crosstalk between mediated IAA29-ARF5-1-ERF3 module provide new insights into pathway.

Language: Английский

Citations

26