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Endocrine-disrupting chemicals (EDCs) and epigenetic regulation in embryonic development: Mechanisms, impacts, and emerging trends

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Toxicology Reports 2025年 14卷

作者： Akanbi, Clinton Ayodeji Rotimi, Damilare Emmanuel Ojo, Adebola Busola Ojo, Oluwafemi Adeleke Good Health and Wellbeing Research Clusters (SDG 03) Bowen University Iwo 232102 Nigeria Phytomedicine Molecular Toxicology and Computational Biochemistry Research Group Biochemistry Programme Bowen University Iwo 232102 Nigeria Department of Biochemistry Landmark University Kwara State Omu-Aran 251101 Nigeria Department of Pharmacology and Pharmaceutical Sciences Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences University of Southern California Los Angeles 90089 CA United States Department of Environmental Management and Toxicology University of Ilesa Osun Ilesa Nigeria

Endocrine-disrupting chemicals (EDCs) are prevalent ecological pollutants that interfere with hormonal systems and pose serious health risks to the public, especially during critical developmental windows. Well-known EDCs, such as bisphenol A (BPA) and phthalates, can alter gene regulation and induce epigenetic modifications that worsen reproductive and developmental disorders. This review explores the intricate relationships that exist among epigenetic mechanisms, EDCs, and embryonic development, with a focus on significant modifications such as DNA methylation, histone modifications, and noncoding rna dynamics that are critical for cellular differentiation. We review the possible health implications of EDC-induced epigenetic changes, focusing on how they could increase susceptibility to diseases. In addition, we provide a critical review of the available treatments aimed at reversing these epigenetic changes and highlight the groundbreaking technologies of high-throughput sequencing and CRISPR-based epigenome editing that are redefining the understanding of EDC effects. This thorough analysis highlights the necessity of efficient regulations that lower EDC exposure as well as the possibility of customized preventative measures to ensure developmental safety. © 2024 The Authors

关键词： DNA methylation Embryonic differentiation Epigenome editing Histone modifications Hormonal disruption noncoding rna Reproductive disorders

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Ornate, large, extremophilic (OLE) rna forms a kink turn necessary for OapC protein recognition and rna function

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JOUrnaL OF BIOLOGICAL CHEMISTRY 2022年第12期298卷 102674页

作者： Lyon, Seth E. Harris, Kimberly A. Odzer, Nicole B. Wilkins, Sarah G. Breaker, Ronald R. Yale Univ Dept Mol Biophys & Biochem New Haven CT 06520 USA Yale Univ Dept Mol Cellular & Dev Biol New Haven CT 06520 USA Yale Univ Howard Hughes Med Inst New Haven CT 06520 USA

Ornate, large, extremophilic (OLE) rnas represent a class of noncoding rnas prevalent in Gram-positive, extremophilic/ anaerobic bacterial species. OLE rnas (-600 nt), whose pre-cise biochemical functions remain mysterious, form an intri-cate secondary structure interspersed with regions of highly conserved nucleotides. In the alkali-halophilic bacterium Ba-cillus halodurans, OLE rna is a component of a ribonucleo-protein (RNP) complex involving at least two proteins named OapA and OapB, but additional components may exist that could point to functional roles for the rna. Disruption of the genes for either OLE rna, OapA, or OapB result in the inability of cells to overcome cold, alcohol, or Mg2+ stresses. In the current study, we used in vivo crosslinking followed by OLE rna isolation to identify the protein YbxF as a potential additional partner in the OLE RNP complex. Notably, a mu-tation in the gene for this same protein was also reported to be present in a strain wherein the complex is nonfunctional. The B. halodurans YbxF (herein renamed OapC) is homologous to a bacterial protein earlier demonstrated to bind kink turn (k -turn) rna structural motifs. In vitro rna-protein binding assays reveal that OLE rna forms a previously unrecognized k -turn that serves as the natural binding site for YbxF/OapC. Moreover, B. halodurans cells carrying OLE rnas with disruptive mutations in the k-turn exhibit phenotypes identical to cells lacking functional OLE RNP complexes. These findings reveal that the YbxF/OapC protein of B. halodurans is important for the formation of a functional OLE RNP complex.

关键词： cold stress ethanol stress noncoding rna ribonucleoprotein complex ribozyme

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Delivery of prostate cancer-associated non-coding rnas within the bone marrow milieu

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JOUrnaL OF REPRODUCTIVE IMMUNOLOGY 2023年第1期156卷 103840-103840页

作者： Takizawa, Toshihiro Noguchi, Syunya Soeta, Satoshi Mikami, Hikaru Kondo, Yukihiro Nippon Med Sch Dept Mol Med & Anat Tokyo Japan Nippon Vet & Life Sci Univ Lab Vet Anat Fac Vet Sci Tokyo Japan Nippon Med Sch Dept Urol Tokyo Japan

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Bibliometric Analysis of ncrna Studies in Diabetes Mellitus With Coronary Heart Disease: A Visualization Approach

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CLINICAL MEDICINE INSIGHTS-ENDOCRINOLOGY AND DIABETES 2024年 17卷

作者： Tang, Yu'e Gu, Rifang Rong, Jidong Nie, Xuqiang Zunyi Med Univ Sch Clin Med Zunyi Peoples R China Zunyi Med Univ Univ Med Off Zunyi Peoples R China Zunyi Med Univ Affiliated Hosp Dept Cardiol Zunyi Peoples R China Minist Educ Key Lab Basic Pharmacal Zunyi Peoples R China Minist Educ Joint Int Res Lab Ethnomed Zunyi Peoples R China Zunyi Med Univ Coll Pharm Zunyi Peoples R China

Objectives: Non-coding rna (ncrna) plays a role in the development of diabetes and coronary heart disease. However, there is limited research on the association between ncrna and these conditions. This study aims to conduct a bibliometric analysis and visualization of existing research to provide a comprehensive reference for future investigation in this ***: We searched the China National Knowledge Infrastructure (CNKI) and Web of Science Core Collection (WoSCC) databases for articles published from 2012 to 2024. We analyzed publication volume, country of origin, authors, and keywords using Microsoft Office Excel, CiteSpace, and ***: A total of 414 papers from 56 countries/regions, involving 298 authors, were analyzed. China had the highest number of publications (177), followed by the USA (90) and Italy (28). The number of publications generally shows an increasing trend. Collaborative research efforts were prevalent, with Katare Rajesh being the most cited author on average. International Journal of Molecular Sciences emerged as the most prolific journal in this field, while the article "Microrna profiling unveils hyperglycaemic memory in the diabetic heart" was identified as the most frequently cited. The analysis of keywords and literature indicates that current research predominantly focuses on the expression and mechanisms of ncrna in disease, as well as its potential as a ***: Research on ncrna in the context of diabetes and coronary heart disease has made notable strides, although it warrants further exploration. Through bibliometric and visual analysis, we elucidate the collaborative relationships among researchers, which can facilitate the identification of potential collaborators. Additionally, we delineate the key areas and emergent trends in this field, providing valuable insights that can guide researchers in selecting future research directions. Tables and pictures are used to show the research status of ncrna

关键词： noncoding rna diabetes mellitus with coronary heart disease bibliometrics micrornas circular rnas long non-coding rnas

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micrornas in cancer chemoresistance: The sword and the shield

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NON-CODING rna RESEARCH 2021年第4期6卷 200-210页

作者： Mondal, Priya Meeran, Syed Musthapa CSIR Cent Food Technol Res Inst Dept Biochem Mysore 570020 Karnataka India Acad Sci & Innovat Res AcSIR Ghaziabad 201002 India

Cancer is a multifactorial disease and one of the leading causes of mortality worldwide. Cancer cells develop multiple strategies to reduce drug sensitivity and eventually lead to chemoresistance. Chemoresistance is initiated either by intrinsic factors or due to the prolonged use of chemotherapeutics as acquired resistance. Further, chemoresistance is also one of the major reasons behind tumor recurrence and metastasis. Therefore, overcoming chemoresistance is one of the primary challenges in cancer therapy. Several mechanisms are involved in chemoresistance. Among them, the key role of ABC transporters and tumor micmenvironment have been well studied. Recently, micrornas (mirnas) regulation in tumor development, metastasis, and chemotherapy has got wider interest due to its role in regulating genes involved in cancer progression and therapy. noncoding rnas, including mirnas, have been associated with the regulation of tumor-suppressor and tumor-promoter genes. Further, mirna can also be used as a reliable diagnostic and prognostic marker to predict the stage and types of cancer. Recent evidences have revealed that mirnas regulation also influences the function of drug transporters and the tumor micmenvironment, which affects chemosensitivity to cancer cells. Therefore, mirnas can be a promising target to reverse back chemosensitivity in cancer cells. This review comprehensively discusses the mechanisms involved in cancer chemoresistance and its regulation by mirnas.

关键词： Cancer noncoding rna Multi-drug resistance Autophagy mirna Hypoxia

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The Pros and Cons of Circular rnas as mirna Sponges

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Biophysics (Russian Federation) 2021年第1期66卷 8-16页

作者： Duk, M.A. Samsonova, M.G. Ioffe Physical Technical Institute St. Petersburg 194021 Russian Federation Peter the Great St. Petersburg Polytechnic University St. Petersburg 195251 Russian Federation

The roles that noncoding rnas play in various cells have been a focus of intense research in recent years. Circular rnas (circrnas) are noncoding rnas that were initially thought to be junk by-products of splicing. Many circrnas have been found to demonstrate important regulatory functions and, in particular, to act as mirna sponges. The function of an mirna sponge was compared with the function of a classic transcription factor (TF)-dependent regulatory loop in terms of efficiency, working rate, and noise characteristics. A circrna with multiple binding sites for mirna was found to act more efficiently than a TF and the respective loop worked faster, but only when the binding sites were not fully saturated with mirna molecules. The noise characteristics of the circrna loop were significantly worse with an increasing number of binding sites. A circrna with one binding site was shown to be inefficient as an mirna sponge. The circrna-mediated regulation was assumed to provide a specific tool to the cell. © 2021, Pleiades Publishing, Inc.

关键词： Keywords: circular rnas mirna mirna sponge noise noncoding rna

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Evolutionary Conservation of rna Secondary Structure

Evolutionary Conservation of RNA Secondary Structure

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作者： Maria Beatriz Walter Costa

noncoding rnas, ncrnas, naturally fold into structures, which allow them to perform their functions in the cell. Evolutionarily close species share structures and functions. This occurs because of shared selective pressures, resulting in conserved groups. Previous efforts in finding functional rnas have been made in detecting conserved structures in genomes or alignments. It may occur that, within a conserved group, species-specific structures arise after species split due to positive selection. Detecting positive selection in ncrnas is a hard problem in biology as well as bioinformatics. To detect positive selection, one should find species-specific structures within a conserved set. This chapter provides protocols to detect and analyze positive selection in ncrna structures with the SSS-test and other free software. less

关键词： Statistical Calculation Conservation Positive selection Evolution noncoding rna Secondary structure

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Use of a combined antibacterial synergy approach and the ANNOgesic tool to identify novel targets within the gene networks of multidrug-resistant Klebsiella pneumoniae

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mSystems 2024年第3期9卷 e0087723页

作者： Lee, Hyunsook Yu, Sung-Huan Shim, Jung Eun Yong, Dongeun Department of Laboratory Medicine Research Institute of Bacterial Resistance Yonsei University College of Medicine Seoul South Korea Brain Korea 21 PLUS Project for Medical Science Yonsei University College of Medicine Seoul South Korea Institute of Precision Medicine College of Medicine National Sun Yat-sen University Kaohsiung Taiwan School of Medicine College of Medicine National Sun Yat-sen University Kaohsiung Taiwan Bioinformatics Collaboration Unit Yonsei Biomedical Research Institute Yonsei University College of Medicine Seoul South Korea

Since the 1980s, the development of new drug classes for the treatment of multidrug-resistant Klebsiella pneumoniae has become limited, highlighting the urgent need for novel antibiotics. To address this challenge, this study aimed to explore the synergistic interactions between chemical compounds and representative antibiotics, such as carbapenem and colistin. The primary objective of this study was not only to mitigate the adverse impact of multidrug-resistant K. pneumoniae on public health but also to establish a sustainable balance among humans, animals, and the environment. Phenotypical measurements were conducted using the broth microdilution technique to determine the drug sensitivity of bacterial strains. Additionally, a genotypical approach was employed, involving traditional rna sequencing analysis to identify differentially expressed genes and the computational ANNOgesic tool to detect noncoding rnas. This study revealed the existence of various pathways and regulatory rna elements that form a functional network. These pathways, characterized by the expression of specific genes, contribute to the combined treatment effect and bacterial survival strategies. The connections between pathways are facilitated by regulatory rna elements that respond to environmental changes. These findings suggest an adaptive response of bacteria to harsh environmental conditions. Copyright © 2024 Lee et al.

关键词： ANNOgesic chemical compound colistin gene network meropenem multidrug-resistant (MDR) noncoding rna rna sequencing synergy

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Exosomal noncoding rnas in Glioma: biological functions and potential clinical applications

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MOLECULAR CANCER 2020年第1期19卷 66-66页

作者： Cheng, Jian Meng, Jinli Zhu, Lei Peng, Yong Sichuan Univ West China Hosp State Key Lab Biotherapy Lab Mol Oncol Chengdu 610041 Peoples R China Sichuan Univ West China Hosp Canc Ctr Chengdu 610041 Peoples R China Sichuan Univ West China Hosp Dept Neurosurg Chengdu Peoples R China Hosp Chengdu Off Peoples Govt Tibetan Autonomous Dept Radiol Chengdu Peoples R China

Gliomas are complex and heterogeneous brain tumors with poor prognosis. Glioma cells can communicate with their surroundings to create a tumor-permissive microenvironment. Exosomes represent a new means of intercellular communication by delivering various bioactive molecules, including proteins, lipids and nucleic acids, and participate in tumor initiation and progression. noncoding rnas (ncrnas) including microrna, long-noncoding rna, and circular rna, account for a large portion of human transcriptome and play important roles in various pathophysiological processes, especially in cancers. In addition, ncrnas can be selectively packaged, secreted and transferred between cells in exosomes and modulate numerous hallmarks of glioma, such as proliferation, invasion, angiogenesis, immune-escape, and treatment resistance. Hence, the strategies of specifically targeting exosomal ncrnas could be attractive therapeutic options. Exosomes are able to cross the blood brain barrier (BBB), and are readily accessible in nearly all types of human biofluids, which make them the promising biomarkers for gliomas. Additionally, given the biocompatibility of exosomes, they can be engineered to deliver therapeutic factors, such as rna, proteins and drugs, to target cells for therapeutic applications. Here, we reviewed current research on the roles of exosomal ncrnas in glioma progression. We also discussed their potential clinical applications as novel biomarkers and therapeutics.

关键词： Exosome Extracellular vesicles noncoding rna Glioma Cancer diagnosis Cancer therapy

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The promising role of noncoding rnas in cancer-associated fibroblasts: an overview of current status and future perspectives

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JOUrnaL OF HEMATOLOGY & ONCOLOGY 2020年第1期13卷 154-154页

作者： Fang, Zengli Xu, Jin Zhang, Bo Wang, Wei Liu, Jiang Liang, Chen Hua, Jie Meng, Qingcai Yu, Xianjun Shi, Si Fudan Univ Shanghai Canc Ctr Dept Pancreat Surg 270 Dong An Rd Shanghai 200032 Peoples R China Fudan Univ Shanghai Med Coll Dept Oncol Shanghai 200032 Peoples R China Shanghai Pancreat Canc Inst Shanghai 200032 Peoples R China Fudan Univ Pancreat Canc Inst Shanghai 200032 Peoples R China

As the most important component of the stromal cell population in the tumor microenvironment (TME), cancer-associated fibroblasts (CAFs) are crucial players in tumor initiation and progression. The interaction between CAFs and tumor cells, as well as the resulting effect, is much greater than initially expected. Numerous studies have shown that noncoding rnas (ncrnas) play an irreplaceable role in this interplay, and related evidence continues to emerge and advance. Under the action of ncrnas, normal fibroblasts are directly or indirectly activated into CAFs, and their metabolic characteristics are changed;thus, CAFs can more effectively promote tumor progression. Moreover, via ncrnas, activated CAFs can affect the gene expression and secretory characteristics of cells, alter the TME and enhance malignant biological processes in tumor cells to contribute to tumor promotion. Previously, ncrna dysregulation was considered the main mechanism by which ncrnas participate in the crosstalk between CAFs and tumor cells. Recently, however, exosomes containing ncrnas have been identified as another vital mode of interaction between these two types of cells, with a more direct and clear function. Gaining an in-depth understanding of ncrnas in CAFs and the complex regulatory network connecting CAFs with tumor cells might help us to establish more effective and safer approaches for cancer therapies targeting ncrnas and CAFs and offer new hope for cancer patients.

关键词： noncoding rna Microrna Long noncoding rna Cancer-associated fibroblasts Tumor microenvironment Cancer Exosome Cell– cell interaction

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