Medical Oncology, Год журнала: 2025, Номер 42(3)
Опубликована: Янв. 24, 2025
Язык: Английский
Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)
Опубликована: Ноя. 26, 2024
Epigenetics governs a chromatin state regulatory system through five key mechanisms: DNA modification, histone RNA remodeling, and non-coding regulation. These mechanisms their associated enzymes convey genetic information independently of base sequences, playing essential roles in organismal development homeostasis. Conversely, disruptions epigenetic landscapes critically influence the pathogenesis various human diseases. This understanding has laid robust theoretical groundwork for developing drugs that target epigenetics-modifying pathological conditions. Over past two decades, growing array small molecule targeting such as methyltransferase, deacetylase, isocitrate dehydrogenase, enhancer zeste homolog 2, have been thoroughly investigated implemented therapeutic options, particularly oncology. Additionally, numerous epigenetics-targeted are undergoing clinical trials, offering promising prospects benefits. review delineates epigenetics physiological contexts underscores pioneering studies on discovery implementation drugs. include inhibitors, agonists, degraders, multitarget agents, aiming to identify practical challenges avenues future research. Ultimately, this aims deepen epigenetics-oriented strategies further application settings.
Язык: Английский
Процитировано
24
Journal of Drug Delivery Science and Technology, Год журнала: 2024, Номер 95, С. 105599 - 105599
Опубликована: Март 26, 2024
Despite considerable progress in patient care, the global incidence of various cancer types continues to rise. Developing safer and more efficient anti-cancer treatment approaches are great interest. In recent decades, nanotechnology has emerged as a promising innovative medical approach for diagnosis treatment. However, nanomedicine advances, it is important understand address challenges. Herein, we identify gaps current understanding effectiveness on clinical outcomes provide an outlook improved application medicine. We discuss use different nanoparticles therapy impact efficiency existing treatments, such chemotherapeutic, anti-angiogenic, immunotherapeutic drugs, radiotherapy. Additionally, update status trials nanoparticle-based treatments provided.
Язык: Английский
Процитировано
19
Molecular Cancer, Год журнала: 2024, Номер 23(1)
Опубликована: Авг. 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.
Язык: Английский
Процитировано
16
Experimental Hematology and Oncology, Год журнала: 2024, Номер 13(1)
Опубликована: Янв. 22, 2024
Abstract Cancer immunotherapy has emerged as a promising strategy in the treatment of colorectal cancer, and relapse after tumor attracted increasing attention. stem cells (CSCs), small subset with self-renewal differentiation capacities, are resistant to traditional therapies such radiotherapy chemotherapy. Recently, CSCs have been proven be driving immunotherapy. However, mutual interactions between cancer niche immune largely uncharacterized. In this review, we focus on CSCs, CSC-immune cell CSC-based Colorectal characterized by robust expression surface markers CD44, CD133 Lgr5; hyperactivation stemness-related signaling pathways, Wnt/β-catenin, Hippo/Yap1, Jak/Stat Notch pathways; disordered epigenetic modifications, including DNA methylation, histone modification, chromatin remodeling, noncoding RNA action. Moreover, express abnormal levels immune-related genes MHC checkpoint molecules mutually interact multiple tumorigenesis-related processes, initiation, maintenance, metastasis drug resistance. To date, many targeting evaluated, monoclonal antibodies, antibody‒drug conjugates, bispecific vaccines adoptive therapy, molecule inhibitors. With development CSC-/niche-targeting technology, well integration multidisciplinary studies, novel that eliminate reverse their immunosuppressive microenvironment expected developed for solid tumors, cancer.
Язык: Английский
Процитировано
12
Journal of Hematology & Oncology, Год журнала: 2024, Номер 17(1)
Опубликована: Сен. 2, 2024
Ferroptosis, characterized by iron-dependent lipid peroxidation, emerges as a promising avenue for hepatocellular carcinoma (HCC) intervention due to its tumor susceptibility. RNA N6-methyladenosine (m6A) modification has been involved in several types of regulated cell death. However, the roles and molecular mechanisms m6A-related regulators HCC ferroptosis remain unclear. By examining series m6A enzymes upon induction or inhibition, we identified METTL16 novel ferroptotic repressor cells. The on development were investigated multiple lines, human organoids, subcutaneous xenografts MYC/Trp53−/− model hepatocyte-specific Mettl16 knockout overexpression mice. underlying mechanism was elucidated with MeRIP/RIP-qPCR, luciferase assay, Co-IP assay Mass Spectrometry. clinical significance relevance evaluated samples. High expression confers resistance cells mouse models, promotes viability progression. Mechanistically, collaborates IGF2BP2 modulate SENP3 mRNA stability an m6A-dependent manner, latter impedes proteasome-mediated ubiquitination degradation Lactotransferrin (LTF) via de-SUMOylation. Elevated LTF facilitates chelation free iron reduces liable pool level. are implicated METTL16-mediated progression anti-ferroptotic effects both vivo vitro. Clinically, positively correlated, high predicts poor prognosis Our study reveals new METTL16-SENP3-LTF signaling axis regulating driving development. Targeting this is strategy sensitizing against HCC.
Язык: Английский
Процитировано
9
Journal of Experimental & Clinical Cancer Research, Год журнала: 2024, Номер 43(1)
Опубликована: Апрель 20, 2024
Refractoriness to surgical resection and chemotherapy makes intrahepatic cholangiocarcinoma (ICC) a fatal cancer of the digestive system with high mortality poor prognosis. Important function invests circRNAs tremendous potential in biomarkers therapeutic targets. Nevertheless, it is still unknown how contribute evolution ICC. CircRNAs paired ICC adjacent tissues were screened by sequencing. To explore impact on development, experiments involving gain loss conducted. Various experimental techniques, including quantitative real-time PCR (qPCR), western blotting, RNA immunoprecipitation (RIP), luciferase reporter assays, pull-down, chromatin (ChIP), ubiquitination assays so employed identify molecular regulatory role circRNAs. Herein, we reported new circRNA, which originates from exon 9 15 SLCO1B3 gene (named circSLCO1B3), orchestrated progression promoting tumor proliferation, metastasis immune evasion. We found that circSLCO1B3 was highly overexpressed related lymphatic metastasis, sizes, differentiation. Mechanically, not only promoted proliferation via miR-502-5p/HOXC8/SMAD3 axis, but also eradicated anti-tumor immunity suppressing ubiquitin-proteasome-dependent degradation PD-L1 E3 ubiquitin ligase SPOP. further methyltransferase like 3 (METTL3) mediated m6A methylation stabilizes its expression. Our findings indicate prognostic marker target patients. Taken together, m6A-modified correlated prognosis enhancing potentiating HOXC8 expression, inducing evasion antagonizing degradation. These results suggest for
Язык: Английский
Процитировано
8
Annals of Hepatology, Год журнала: 2025, Номер unknown, С. 101776 - 101776
Опубликована: Янв. 1, 2025
Deregulation of m
Язык: Английский
Процитировано
1
Cell Death Discovery, Год журнала: 2025, Номер 11(1)
Опубликована: Янв. 27, 2025
Abstract Methyltransferase-like 1 (METTL1)-mediated m7G modification is a common occurrence in various RNA species, including mRNAs, tRNAs, rRNAs, and miRNAs. Recent evidence suggests that this linked to the development of several cancers, making it promising target for cancer therapy. However, specific role cutaneous squamous cell carcinoma (cSCC) not well understood. In study, we observed conspicuously elevated levels METTL1 cSCC tumors lines. Inhibiting led reduced survival, migration, invasion, xenograft tumor growth cells. Mechanistically, through combination sequencing, methylated immunoprecipitation (MeRIP)-qPCR, mRNA stability assays, discovered responsible ATF4 mRNA, leading increased expression ATF4. Importantly, demonstrated dependent on methyltransferase activity METTL1. Additionally, positive association between tumors. Intriguingly, restoring cells only promoted glycolysis but also reversed anti-tumor effects knockdown. conclusion, our results underscore critical tumorigenesis, suggesting future therapies.
Язык: Английский
Процитировано
1
European journal of medical research, Год журнала: 2025, Номер 30(1)
Опубликована: Фев. 12, 2025
The significance of m6A modifications in several biological processes has been increasingly recognized, particularly the context cancer. For instance, gastric cancer (GC) have significantly implicated tumor progression, metastasis, and treatment resistance. GC is characterized by differential expression regulators. High writers such as METTL3 WTAP are associated with poor prognosis aggressive clinical features. Conversely, low METTL14 linked to worse outcomes, whereas elevated levels demethylases, FTO ALKBH5, correlate better survival rates. These regulators influence cellular functions, including proliferation, invasion, migration, glycolysis, chemotherapy resistance, thereby affecting growth therapeutic outcomes. assessment modification patterns profiles m6A-related genes hold substantial potential for improving diagnosis GC. In this review, we provide an updated comprehensive summary role GC, emphasizing their molecular mechanisms, significance, translational applications developing novel diagnostic strategies.
Язык: Английский
Процитировано
1
Molecular Carcinogenesis, Год журнала: 2025, Номер unknown
Опубликована: Фев. 17, 2025
ABSTRACT METTL1, a well‐established RNA methyltransferase for the N(7)‐methylguanosine (m7G) methylation modification, is responsible human tumorigenesis. Here, we aimed to examine activity and molecular determinants of METTL1 in colorectal cancer (CRC) development. ribosomal processing 9 (RRP9) mRNA analysis was performed by quantitative PCR. Protein expression detected immunoblotting immunohistochemistry (IHC). Cell sphere formation, invasion, proliferation were assessed transwell, MTT assays, respectively. migration tested transwell wound healing assays. Subcutaneous xenografts produced analyze role vivo. The influence m7G stability RRP9 evaluated methylated immunoprecipitation (MeRIP) assay Actinomycin D (Act D) treatment, highly expressed CRC tumors cell lines. depletion suppressed proliferation, invasiveness, migratory ability, formation potential vitro, while increased had opposite effects. positively correlated with CRC. Mechanistically, promoted mediating its methylation, regulated PI3K/AKT signaling RRP9. Increased partially reversed suppressive effects on phenotypes vitro. impeded growth HCT‐116 subcutaneous vivo Our observations identified as crucial protumorigenic factor drive growth, metastasis, stemness cells through RRP9, offering new targets combating
Язык: Английский
Процитировано
1