Post‐translational modifications of histones: Mechanisms, biological functions, and therapeutic targets

MedComm, Journal Year: 2023, Volume and Issue: 4(3)

Published: May 20, 2023

Abstract Histones are DNA‐binding basic proteins found in chromosomes. After the histone translation, its amino tail undergoes various modifications, such as methylation, acetylation, phosphorylation, ubiquitination, malonylation, propionylation, butyrylation, crotonylation, and lactylation, which together constitute “histone code.” The relationship between their combination biological function can be used an important epigenetic marker. Methylation demethylation of same residue, acetylation deacetylation, phosphorylation dephosphorylation, even methylation different residues cooperate or antagonize with each other, forming a complex network. Histone‐modifying enzymes, cause numerous codes, have become hot topic research on cancer therapeutic targets. Therefore, thorough understanding role post‐translational modifications (PTMs) cell life activities is very for preventing treating human diseases. In this review, several most thoroughly studied newly discovered PTMs introduced. Furthermore, we focus histone‐modifying enzymes carcinogenic potential, abnormal modification sites tumors, multiple essential molecular regulation mechanism. Finally, summarize missing areas current point out direction future research. We hope to provide comprehensive promote further field.

Language: Английский

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Writers, readers, and erasers RNA modifications and drug resistance in cancer

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

Published: Aug. 30, 2024

Drug resistance in cancer cells significantly diminishes treatment efficacy, leading to recurrence and metastasis. A critical factor contributing this is the epigenetic alteration of gene expression via RNA modifications, such as N6-methyladenosine (m6A), N1-methyladenosine (m1A), 5-methylcytosine (m5C), 7-methylguanosine (m7G), pseudouridine (Ψ), adenosine-to-inosine (A-to-I) editing. These modifications are pivotal regulating splicing, translation, transport, degradation, stability. Governed by "writers," "readers," "erasers," impact numerous biological processes progression, including cell proliferation, stemness, autophagy, invasion, apoptosis. Aberrant can lead drug adverse outcomes various cancers. Thus, targeting modification regulators offers a promising strategy for overcoming enhancing efficacy. This review consolidates recent research on role prevalent resistance, with focus m6A, m1A, m5C, m7G, Ψ, A-to-I Additionally, it examines regulatory mechanisms linked underscores existing limitations field.

Language: Английский

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Fatty Acid Metabolism in Ovarian Cancer: Therapeutic Implications

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(4), P. 2170 - 2170

Published: Feb. 16, 2022

Ovarian cancer is the most malignant gynecological tumor. Previous studies have reported that metabolic alterations resulting from deregulated lipid metabolism promote ovarian aggressiveness. Lipid involves oxidation of fatty acids, which leads to energy generation or new metabolite synthesis. The upregulation acid synthesis and related signaling tumor cell proliferation migration, and, consequently, lead poor prognosis. Fatty acid-mediated in microenvironment (TME) modulates immunity by regulating immune cells, including T B macrophages, natural killer play essential roles survival. Here, types sources acids their interactions with TME been reviewed. Additionally, this review focuses on role suggests pathways are potential therapeutic targets for cancer.

Language: Английский

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Long non-coding RNAs (lncRNAs); roles in tumorigenesis and potentials as biomarkers in cancer diagnosis

Experimental Cell Research, Journal Year: 2022, Volume and Issue: 418(2), P. 113294 - 113294

Published: July 20, 2022

Language: Английский

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CRABP2 affects chemotherapy resistance of ovarian cancer by regulating the expression of HIF1α

Cell Death and Disease, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 9, 2024

Abstract Ovarian cancer is the most lethal malignancy among gynecologic cancers, and primary secondary chemotherapy resistance one of important reasons for poor prognosis ovarian patients. However, specifics to in remain unclear. Herein, we find that expression level cellular retinoic acid binding protein 2 (CRABP2) up-regulated drug-resistant tissues cell lines, levels CRABP2 epithelial are closely related tumor clinical stage patients’ prognosis, suggesting plays an role progression corresponding ability chemotherapy. With in-depth study, demonstrates high metabolic activity cells, all-trans exacerbates this activity. Further molecular mechanism exploration experiments show not only up-regulates HIF1α, but also increases localization HIF1α nucleus. In knocking down can block drugs cells. Taken together, our findings suggest first time affects by regulating HIF1α. This study provides a possible drug target treatment cancer.

Language: Английский

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Mechanistic insights into epithelial-mesenchymal transition mediated cisplatin resistance in ovarian cancer

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 24, 2025

Epithelial-mesenchymal transition (EMT) is designated as one of the prime causes chemoresistance in many cancers. In our previous study we established that cisplatin resistance ovarian cancer (OC) associated with EMT using sensitive OV90 cells and its resistant counterparts OV90CisR1 OV90CisR2. this study, revealed through RNAseq analysis ITGA1 can play essential part mediated OC. We found large number related terms predominant top gene ontologies (GO). also Extracellular matrix (ECM) actin cytoskeleton genes highly altered cells. This was further confirmed by protein-protein interaction (PPI) where identified core ECM components e.g., collagen, fibronectin, metalloproteases integrins possessed most interactions. The pathway Wnt signaling leading pathway. Since have significant signaling, focused on among which, ITGA1, ITGA6, ITGA11 ITGAV were primarily altered. validated results western blotting expressed Additionally, high ABCA5 (efflux transporter) expression supports proposition. β-catenin confirming activity. Further, induced xenograft tumors nude mice. histopathological aggressive nature showed presence necrotic which could be implicated to EMT. Finally, immunohistochemical staining protein tumor.

Language: Английский

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Exosomes in diagnostic and therapeutic applications of ovarian cancer

Journal of Ovarian Research, Journal Year: 2024, Volume and Issue: 17(1)

Published: May 25, 2024

Abstract Ovarian cancer accounts for more deaths than any other female reproductive tract cancer. The major reasons the high mortality rates include delayed diagnoses and drug resistance. Hence, improved diagnostic therapeutic options ovarian are a pressing need. Extracellular vesicles (EVs), that exosomes provide hope in both aspects. They natural lipid nanovesicles secreted by all cell types carry molecules reflect status of parent cell. This facilitates their potential use as biomarkers an early diagnosis. Additionally, EVs can be loaded with exogenous cargo, have features such stability favorable pharmacokinetic properties. makes them ideal tumor-targeted delivery biological moieties. International Society Vesicles (ISEV) based on Minimal Information Studies (MISEV) recommends usage term “small extracellular (sEVs)” includes particles 30–200 nm size. However, majority studies reported literature relevant to this review used “exosomes”. Therefore, will “exosomes” interchangeably sEVs consistency avoid confusion readers. review, initially summarizes different isolation detection techniques developed study cancer-derived these diagnosis devastating disease. It addresses role exosome contents pathogenesis cancer, discusses strategies limit exosome-mediated progression, provides therapy Finally, it states future research directions essential needed successfully transition from laboratory gynecologic-oncology clinic.

Language: Английский

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The Application of Nanoparticle‐Based Imaging and Phototherapy for Female Reproductive Organs Diseases

Small, Journal Year: 2023, Volume and Issue: unknown

Published: May 8, 2023

Various female reproductive disorders affect millions of women worldwide and bring many troubles to women's daily life. Let alone, gynecological cancer (such as ovarian cervical cancer) is a severe threat most lives. Endometriosis, pelvic inflammatory disease, other chronic diseases-induced pain have significantly harmed physical mental health. Despite recent advances in the field, existing challenges are still enormous such personalization difficulty diagnosing early cancers, antibiotic resistance infectious diseases, etc. To confront challenges, nanoparticle-based imaging tools phototherapies that offer minimally invasive detection treatment tract-associated pathologies indispensable innovative. Of late, several clinical trials also been conducted using nanoparticles for tract infections targeted drug delivery, cellular therapeutics. However, these nanoparticle nascent due body's delicate complex system. The present review comprehensively focuses on emerging applications, which hold promise improved diagnosis effective treatments various organ diseases.

Language: Английский

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A methylation- and immune-related lncRNA signature to predict ovarian cancer outcome and uncover mechanisms of chemoresistance

Journal of Ovarian Research, Journal Year: 2023, Volume and Issue: 16(1)

Published: Sept. 6, 2023

Abstract Tumor-associated lncRNAs regulated by epigenetic modification switches mediate immune escape and chemoresistance in ovarian cancer (OC). However, the underlying mechanisms concrete targets have not been systematically elucidated. Here, we discovered that methylation modifications played a significant role regulating cell infiltration sensitizing OC to chemotherapy modulating immune-related (irlncRNAs), which represent tumor status. Through deep analysis of TCGA database, prognostic risk model incorporating four methylation-related (mrlncRNAs) irlncRNAs was constructed. Twenty-one mrlncRNA/irlncRNA pairs were identified significantly related overall survival (OS) patients. Subsequently, selected construct signature predictive OS indicative infiltration, verified robustness an internal validation set. The score independent factor for prognosis, demonstrated via multifactorial Cox regression nomogram. Moreover, scores negatively expression CD274, CTLA4, ICOS, LAG3, PDCD1, PDCD1LG2 correlated with CD8 + , CD4 Treg tumor-infiltrating cells. In addition, high-risk associated higher IC50 value cisplatin, worse clinical outcome. Next, competing endogenous RNA (ceRNA) network signaling pathway controlling T cells explored based on lncRNA model, suggested potential therapeutic target immunotherapy. Overall, this study constructed pairing mrlncRNAs revealed critical FTO/RP5-991G20.1/hsa-miR-1976/MEIS1 function enhancing anticancer therapy.

Language: Английский

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Emerging Roles of m6A RNA Methylation Regulators in Gynecological Cancer

Frontiers in Oncology, Journal Year: 2022, Volume and Issue: 12

Published: Jan. 28, 2022

Gynecological cancers seriously affect the reproductive system of females; diseases include ovarian tumors, uterine endometrial cancers, cervical and vulva vaginal tumors. At present, diagnosis methods gynecological cancer are insufficiently sensitive specific, leading to failure early disease detection. N6-methyladenosine (m6A) plays various biological functions in RNA modification is currently studied extensively. m6A controls fate transcripts regulates metabolism processes through interaction methyltransferase ("writer") demethylase ("erasers") binding protein decoding methylation ("readers"). In field epigenetics, a dynamic process reversible regulation target its regulatory factors. It an important role many diseases, especially cancer. However, gynecologic has not been fully investigated. Thus, we review mechanism, functions, therapeutic prospects regulators cancers.

Language: Английский

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