Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Год журнала: 2023, Номер 1878(6), С. 188972 - 188972
Опубликована: Авг. 26, 2023
Язык: Английский
Drug Resistance Updates, Год журнала: 2022, Номер 66, С. 100916 - 100916
Опубликована: Дек. 29, 2022
Язык: Английский
Процитировано
158
Journal of Experimental & Clinical Cancer Research, Год журнала: 2022, Номер 41(1)
Опубликована: Окт. 20, 2022
Ferroptosis is a novel form of iron-dependent cell death and participates in the malignant progression glioblastoma (GBM). Although circular RNAs (circRNAs) are found to play key roles ferroptosis via several mechanisms, including regulating iron metabolism, glutathione lipid peroxidation mitochondrial-related proteins, there many circRNAs need be found, they may become new molecular treatment target GBM.The expression levels circLRFN5, PRRX2 GCH1 were detected by qPCR, western blotting, immunohistochemistry. Lentiviral-based infections used overexpress or knockdown these molecules glioma stem cells (GSCs). The biological functions on GSCs MTS (3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H tetrazolium), 5-ethynyl-20-deoxyuridine (EdU) incorporation assay, transwell, neurosphere formation assays, Extreme Limiting Dilution Analysis (ELDA) xenograft experiments. content was BODIPY 581/591 C11 (GSH) assay malondialdehyde (MDA) assay. mechanisms among studied RNA immunoprecipitation pull-down ubiquitination dual-luciferase reporter chromatin assay.We circRNA circLRFN5 downregulated GBM associated with patients' poor prognosis. CircLRFN5 overexpression inhibits viabilities, proliferation, neurospheres formation, stemness tumorigenesis inducing ferroptosis. Mechanistically, binds protein promotes its degradation ubiquitin-mediated proteasomal pathway. can transcriptionally upregulate GSCs, which suppressor generating antioxidant tetrahydrobiopterin (BH4).Our study as tumor-suppressive identified role GBM. potential biomarker for therapies ferroptosis-dependent therapy
Язык: Английский
Процитировано
88
Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)
Опубликована: Дек. 10, 2023
Abstract Ferroptosis, a unique modality of cell death with mechanistic and morphological differences from other modes, plays pivotal role in regulating tumorigenesis offers new opportunity for modulating anticancer drug resistance. Aberrant epigenetic modifications posttranslational (PTMs) promote resistance, cancer progression, metastasis. Accumulating studies indicate that can transcriptionally translationally determine vulnerability to ferroptosis functions as driver nervous system diseases (NSDs), cardiovascular (CVDs), liver diseases, lung kidney diseases. In this review, we first summarize the core molecular mechanisms ferroptosis. Then, roles processes, including histone PTMs, DNA methylation, noncoding RNA regulation such phosphorylation, ubiquitination, SUMOylation, acetylation, ADP-ribosylation, are concisely discussed. The PTMs genesis cancers, NSD, CVDs, well application PTM modulators therapy these then discussed detail. Elucidating mediated by will facilitate development promising combination therapeutic regimens containing or PTM-targeting agents inducers be used overcome chemotherapeutic resistance could prevent addition, highlight potential approaches chemoresistance halt
Язык: Английский
Процитировано
72
Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)
Опубликована: Фев. 2, 2024
Abstract Alternative splicing (AS) serves as a pivotal mechanism in transcriptional regulation, engendering transcript diversity, and modifications protein structure functionality. Across varying tissues, developmental stages, or under specific conditions, AS gives rise to distinct splice isoforms. This implies that these isoforms possess unique temporal spatial roles, thereby associating with standard biological activities diseases. Among these, AS-related RNA-binding proteins (RBPs) play an instrumental role regulating alternative events. Under physiological the diversity of mediated by influences structure, function, interaction, localization proteins, participating differentiation development array tissues organs. pathological alterations are linked various diseases, particularly cancer. These changes can lead gene patterns, culminating loss For instance, cancer, abnormalities RBPs may result aberrant expression cancer-associated genes, promoting onset progression tumors. also associated numerous neurodegenerative diseases autoimmune Consequently, study across different holds significant value. review provides detailed account recent advancements tissue which aids deepening understanding complexity offers new insights methodologies for precision medicine.
Язык: Английский
Процитировано
71
Molecular Cancer, Год журнала: 2023, Номер 22(1)
Опубликована: Март 1, 2023
Abstract N6-methyladenosine (m 6 A) methylation is the most universal internal modification in eukaryotic mRNA. With elaborate functions executed by m A writers, erasers, and readers, modulation involved myriad physiological pathological processes. Extensive studies have demonstrated diverse tumours, with effects on tumorigenesis, metastasis, resistance. Recent evidence has revealed an emerging role of tumour immunoregulation, divergent patterns been microenvironment. To depict regulatory immune microenvironment (TIME) its effect evasion, this review focuses TIME, which characterized hypoxia, metabolic reprogramming, acidity, immunosuppression, outlines A-regulated TIME evasion under stimuli. Furthermore, anti-tumour cells are summarized.
Язык: Английский
Процитировано
56
Molecular Cancer, Год журнала: 2023, Номер 22(1)
Опубликована: Авг. 15, 2023
Abstract Glycolytic reprogramming is one of the most important features cancer and plays an integral role in progression cancer. In cells, changes glucose metabolism meet needs self-proliferation, angiogenesis lymphangiogenesis, metastasis, also affect immune escape, prognosis evaluation therapeutic effect The n6-methyladenosine (m6A) modification RNA widespread eukaryotic cells. Dynamic reversible m6A modifications are widely involved regulation stem cell renewal differentiation, tumor therapy resistance, microenvironment, metabolism. Lately, more evidences show that can glycolysis process tumors a variety ways to regulate biological behavior tumors. this review, we discussed genesis development, elaborated detail profound impact on different by regulating glycolysis. We believe modified has great significance potential for treatment.
Язык: Английский
Процитировано
43
Clinical and Translational Medicine, Год журнала: 2023, Номер 13(10)
Опубликована: Окт. 1, 2023
Background N6-methyladenosine (m6A), the most prevalent internal mRNA modification in eukaryotes, is added by m6A methyltransferases, removed demethylases and recognised m6A-binding proteins. This significantly influences carious facets of RNA metabolism plays a pivotal role cellular physiological processes. Main body Pre-mRNA alternative splicing, process that generates multiple splice isoforms from multi-exon genes, contributes to protein diversity mammals. Moreover, presence crosstalk between with modifications on pre-mRNAs exerting regulatory control, has been established. The modulates splicing patterns recruiting specific RNA-binding proteins (RBPs) regulate or directly influencing interaction RBPs their target RNAs. Conversely, can impact deposition recognition mRNAs. integration expanded scope therapeutic strategies for cancer treatment, while offers novel insights into mechanistic methylation initiation progression. Conclusion review aims highlight biological functions machinery its implications tumourigenesis. Furthermore, we discuss clinical relevance understanding m6A-dependent tumour therapies.
Язык: Английский
Процитировано
41
Frontiers in Immunology, Год журнала: 2022, Номер 13
Опубликована: Окт. 19, 2022
Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women reproductive age. miR-93-5p has been reported to be elevated granulosa cells PCOS patients. However, mechanism by which drives cell (GC) progression remains unclear. Thus, this study focuses on roles and mechanisms GCs PCOS. Methods KGN have similar ovarian physiological characteristics are used function regulatory GCs. In study, were transfected with si-NC, si-miR93-5p, oe-NC oe-miR93-5p. A counting kit-8 assay, flow cytometry western blotting performed observe proliferation apoptosis different groups. Subsequently, levels reactive oxygen species, malondialdehyde, GPX4, SLC7A11 Nrf2, indicators ferroptosis, measured a dihydroethidium fluorescent dye probe, biochemical kit, reverse transcription quantitative polymerase chain reaction. Ultimately, bioinformatic analysis experimental methods examine interaction between NF-κB signaling pathway. Results was upregulated Overexpression promoted ferroptosis cells, while knockdown showed effect. Biological subsequent experiments demonstrated that negatively regulates NF- κB Conclusion promotes GC regulating Silencing protects against dysfunction. Our identified as new molecular target for improving
Язык: Английский
Процитировано
66
Materials Today Bio, Год журнала: 2022, Номер 17, С. 100503 - 100503
Опубликована: Ноя. 24, 2022
A lack of promising targets leads to poor prognosis in patients with lung adenocarcinoma (LUAD). Therefore, it is urgent identify novel therapeutic targets. The importance the N6-methyladenosine (m6A) RNA modification has been demonstrated various types tumors; however, knowledge m6A-related proteins LUAD still limited. Here, we found that insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3), an m6A reader protein, highly expressed and associated prognosis. IGF2BP3 desensitizes ferroptosis (a new form regulated cell death) a manner dependent on its reading domain capacity m6A-methylated mRNAs encoding anti-ferroptotic factors, including but not limited glutathione peroxidase 4 (GPX4), solute carrier family member (SLC3A2), acyl-CoA synthetase long chain (ACSL3), ferritin heavy 1 (FTH1). After overexpression, expression levels stabilities these factors were successfully sustained. Notably, significant correlations between SLC3A2, ACSL3, revealed clinical specimens, further establishing essential role desensitizing ferroptosis. Inducing gradually accepted as alternative strategy treat tumors. Thus, could be potential target for future development biomaterial-associated anti-tumor drugs.
Язык: Английский
Процитировано
60
Molecular Cancer, Год журнала: 2022, Номер 21(1)
Опубликована: Дек. 14, 2022
Abstract Cancer drug resistance represents the main obstacle in cancer treatment. Drug-resistant cancers exhibit complex molecular mechanisms to hit back therapy under pharmacological pressure. As a reversible epigenetic modification, N 6 -methyladenosine (m A) RNA modification was regarded be most common modification. methyltransferases (writers), demethylases (erasers), and m A-binding proteins (readers) are frequently disordered several tumors, thus regulating expression of oncoproteins, enhancing tumorigenesis, proliferation, development, metastasis. The review elucidated underlying role A resistance. Alteration affected efficacy by restructuring multidrug efflux transporters, drug-metabolizing enzymes, anticancer targets. Furthermore, variation resulted DNA damage repair, downstream adaptive response (apoptosis, autophagy, oncogenic bypass signaling), cell stemness, tumor immune microenvironment, exosomal non-coding RNA. It is highlighted that small molecules targeting regulators have shown significant potential for overcoming different categories. Further inhibitors activators A-modified expected provide novel drugs, delivering therapeutic addressing challenge clinical
Язык: Английский
Процитировано
52