HSPB1 facilitates chemoresistance through inhibiting ferroptotic cancer cell death and regulating NF-κB signaling pathway in breast cancer

Cell Death and Disease, Год журнала: 2023, Номер 14(7)

Опубликована: Июль 15, 2023

Chemoresistance is one of the major causes therapeutic failure and poor prognosis for breast cancer patients, especially triple-negative patients. However, underlying mechanism remains elusive. Here, we identified novel functional roles heat shock protein beta-1 (HSPB1), regulating chemoresistance ferroptotic cell death in cancer. Based on TCGA GEO databases, HSPB1 expression was upregulated tissues associated with which considered an independent prognostic factor Functional assays revealed that could promote growth metastasis vitro vivo. Furthermore, facilitated doxorubicin (DOX) resistance through protecting cells from drug-induced ferroptosis. Mechanistically, bind Ikβ-α its ubiquitination-mediated degradation, leading to increased nuclear translocation activation NF-κB signaling. In addition, overexpression led enhanced secretion IL6, further progression. These findings upregulation might be a key driver progression ferroptosis while targeting effective strategy against

Язык: Английский

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Crosstalk between ferroptosis and cuproptosis: From mechanism to potential clinical application

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 171, С. 116115 - 116115

Опубликована: Янв. 5, 2024

Ferroptosis and cuproptosis, regulated forms of cell death resulting from metal ion accumulation, are closely related in terms occurrence, metabolism, signaling pathways, drug resistance. Notably, it is now understood that these processes play crucial roles regulating physiological pathological processes, especially tumor development. Consequently, ferroptosis cuproptosis have gained increasing significance as potential targets for anti-cancer This article systematically outlines the molecular mechanisms cross-talk components both elucidating their impacts on cancer. Furthermore, investigates clinical perspective targeted cancer chemotherapy, immunotherapy, radiotherapy. Our discussion extends to a comparative analysis nanoparticles developed based cancer, contrasting them with current conventional therapies. Opportunities challenges treatment explored, emphasizing therapeutic direction co-targeting cuproptosis. The also attempts analyze applications this approach while summarizing existing barriers require overcoming.

Язык: Английский

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The emerging role of ferroptosis in female reproductive disorders

Biomedicine & Pharmacotherapy, Год журнала: 2023, Номер 166, С. 115415 - 115415

Опубликована: Сен. 4, 2023

Iron, as an essential trace element for the organism, is vital maintaining organism's health. Excessive iron can promote reactive oxygen species (ROS) accumulation, thus damaging cells and tissues. Ferroptosis a novel form of programmed cell death distinguished by overload lipid peroxidation, which unique from autophagy, apoptosis necrosis, more studies are focusing on ferroptosis. Recent evidence suggests that ferroptosis associated with development female reproductive disorders (FRDs), including polycystic ovary syndrome (PCOS), premature ovarian insufficiency (POI), endometriosis (EMs), cancer (OC), preeclampsia (PE) spontaneous abortion (SA). Pathways genes may participate in processes regulate granulosa proliferation secretion, oocyte development, reserve function, early embryonic placental oxidative stress. However, its exact mechanism has not been fully revealed. Therefore, our review systematically elaborates occurrence research progress FRDs, view to providing literature references clinical targeting -related pathways regulatory factors management FRDs.

Язык: Английский

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Inhibition of NF-κB signaling unveils novel strategies to overcome drug resistance in cancers

Drug Resistance Updates, Год журнала: 2024, Номер 73, С. 101042 - 101042

Опубликована: Янв. 4, 2024

Drug resistance in cancer remains a major challenge oncology, impeding the effectiveness of various treatment modalities. The nuclear factor-kappa B (NF-κB) signaling pathway has emerged as critical player development drug cells. This comprehensive review explores intricate relationship between NF-κB and cancer. We delve into molecular mechanisms through which activation contributes to against chemotherapeutic agents, targeted therapies, immunotherapies. Additionally, we discuss potential strategies overcome this by targeting signaling, such small molecule inhibitors combination therapies. Understanding multifaceted interactions is crucial for more effective strategies. By dissecting complex network NF-κB, hope shed light on novel therapeutic approaches that can enhance outcomes, ultimately improving prognosis patients. aims provide overview current state knowledge its role resistance, offering insights may guide future research interventions fight

Язык: Английский

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Decreased miR-128-3p in serum exosomes from polycystic ovary syndrome induces ferroptosis in granulosa cells via the p38/JNK/SLC7A11 axis through targeting CSF1

Cell Death Discovery, Год журнала: 2025, Номер 11(1)

Опубликована: Фев. 18, 2025

Abstract Increasing evidence suggests that non-coding small RNAs (miRNAs) carried by exosomes (EXOs) play important roles in the development and treatment of polycystic ovary syndrome (PCOS). In this study, we demonstrate PCOS mouse serum-derived EXOs promote granulosa cells (GCs) ferroptosis, induce occurrence a PCOS-like phenotype vivo. Notably, EXO miRNA sequencing combined with vitro gain- loss-of-function assays revealed miR-128-3p, which is absent mice PCOS, regulates lipid peroxidation GC sensitivity to ferroptosis inducers. Mechanistically, overexpression CSF1 , direct target reversed anti-ferroptotic effect miR-128-3p. Conversely, induction was mitigated -downregulated GCs. Furthermore, demonstrated miR-128-3p inhibition activates p38/JNK pathway via leading NRF2-mediated down-regulation SLC7A11 transcription, triggers iron overload. Moreover, intrathecal AgomiR injection into ovaries ameliorated characteristics restored fertility letrozole-induced mice. The study reveals pathological mechanisms based on circulating provides first ovarian This discovery expected provide promising therapeutic targets for PCOS.

Язык: Английский

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Selenium deficiency induced inflammation and apoptosis via NF-κB and MAPKs pathways in muscle of common carp (Cyprinus carpio L.)

Fish & Shellfish Immunology, Год журнала: 2023, Номер 138, С. 108847 - 108847

Опубликована: Май 23, 2023

Язык: Английский

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Ovarian ferroptosis induced by androgen is involved in pathogenesis of PCOS

Human Reproduction Open, Год журнала: 2024, Номер 2024(2)

Опубликована: Янв. 1, 2024

Abstract STUDY QUESTION Does ovarian ferroptosis play an active role in the development of polycystic ovary syndrome (PCOS)? SUMMARY ANSWER Increased was present PCOS ovaries and inhibition with ferrostatin-1 (Fer-1) ameliorated morphology anovulation. WHAT IS KNOWN ALREADY Programmed cell death plays a fundamental follicle development. However, types mechanisms involved are yet to be elucidated. Ferroptosis is recently discovered iron-dependent programmed death. Impaired iron metabolism have been observed women PCOS, main cause anovulatory infertility. Additionally, previous studies reported that abnormal expression noncoding RNA may promote immortalized granulosa lines. little known about whether increased there insufficient direct evidence for underlying mechanism. Moreover, effect Fer-1 remains unclear. DESIGN, SIZE, DURATION evaluated human cells (hGCs) from non-PCOS (n = 6–16) 7–18) patients. The experimental study completed vitro using primary hGCs undergoing IVF. Improvements indicators following were investigated dehydroepiandrosterone (DHEA)-induced rat model 8 per group). PARTICIPANTS/MATERIALS, SETTING, METHODS Ovarian ways: by detecting concentrations via ELISA fluorescent probes; measuring malondialdehyde (MDA) ELISA; assessing ferroptosis-related protein abundance western blotting; observing mitochondrial transmission electron microscopy; determining viability. Primary collected They treated dihydrotestosterone (DHT) 24 h. DHT on examined presence or absence small interfering RNA-mediated knockdown putative receptor coregulator signaling molecules. progression explored vivo rats. DHEA-induced inhibitor, Fer-1, oocytes metaphase II counted after stimulation. rats inducer, RSL3, further explore ferroptosis. testosterone, FSH, LH assessed. MAIN RESULTS AND THE ROLE OF CHANCE detected patients PCOS. Fe2+ (P < 0.05) MDA 0.05), upregulated nuclear coactivator 4 levels, downregulated ferritin heavy chain 1 (FTH1) glutathione peroxidase (GPX4) proteins 0.05 versus control). shown induce activation NOCA4-dependent ferritinophagy. cluster traits including impaired glucose tolerance, irregular estrous cycles, reproductive hormone dysfunction, hyperandrogenism, ovaries, anovulation, oocyte quality 0.05). Treating RSL3 resulted hyperandrogenism LARGE-SCALE DATA N/A. LIMITATIONS, REASONS FOR CAUTION Although ovarian-targeted more targeted treatment cycle between require exploration. since shows high heterogeneity, it important investigate increases all WIDER IMPLICATIONS FINDINGS Androgen-induced appears pathogenesis which potentially makes promising target FUNDING/COMPETING INTEREST(S) This supported National Key R&D Program China (2023YFC2705500, 2023YFC2705505, 2019YFA0802604), Natural Science Foundation (No. 82130046, 82320108009, 82101708, 82101747, 82001517), Shanghai leading talent program, Innovative research team high-level local universities SHSMU-ZLCX20210201, No. SSMU-ZLCX20180401), Jiaotong University School Medicine, Affiliated Renji Hospital Clinical Research Innovation Cultivation Fund (RJPY-DZX-003) Municipal Education Commission—Gaofeng Medicine Grant Support 20161413), Shanghai’s Top Priority Center Construction Project (2023ZZ02002), Three-Year Action Plan Strengthening Public Health System (GWVI-11.1-36). authors report no competing interests.

Язык: Английский

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From Pathophysiology to Treatment: The Role of Ferroptosis in PCOS

Frontiers in Bioscience-Landmark, Год журнала: 2025, Номер 30(2)

Опубликована: Фев. 17, 2025

Polycystic ovary syndrome (PCOS) is a prevalent gynecological endocrine and metabolic disorder in women, with an incidence rate of 10-13%. The etiology PCOS multifaceted, involving genetic predisposition, environmental influences, lifestyle factors, dysregulation. Iron, critical mineral, not only plays role regulating female physiological functions the progression but also requires careful management to avoid deficiency. However, excess iron can trigger ferroptosis, form nonapoptotic cell death characterized by accumulation lipid peroxides. While numerous studies have explored ferroptosis patients animal models, precise mechanisms therapeutic implications remain inadequately understood. This review seeks elucidate pathophysiology contributory factors ferroptosis. Additionally, we examine diverse manifestations evaluate its role. Furthermore, introduce ferroptosis-related traditional Chinese medicines that may enhance understanding pathogenesis aid development targeted therapies for PCOS.

Язык: Английский

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Aconine attenuates osteoclast-mediated bone resorption and ferroptosis to improve osteoporosis via inhibiting NF-κB signaling

Frontiers in Endocrinology, Год журнала: 2023, Номер 14

Опубликована: Ноя. 13, 2023

Osteoporosis (OP), a prevalent public health concern primarily caused by osteoclast-induced bone resorption, requires potential therapeutic interventions. Natural compounds show as therapeutics for postmenopausal OP. Emerging evidence from in vitro osteoclastogenesis assay suggests that aconine (AC) serves an osteoclast differentiation regulator without causing cytotoxicity. However, the vivo functions of AC various OP models need clarification. To address this, we administered intraperitoneal injections to ovariectomy (OVX)-induced mice 8 weeks and found effectively reversed phenotype OVX mice, leading reduction vertebral loss restoration high turnover markers. Specifically, significantly suppressed decreasing expression osteoclast-specific genes such NFATc1 , c-Fos Cathepsin K Mmp9 . Importantly, can regulate ferroptosis suppressing Gpx4 upregulating Acsl4, which is achieved through inhibition phosphorylation I-κB p65 NF-κB signaling pathway. These findings suggest option managing signaling-mediated formation.

Язык: Английский

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FASN contributes to ADM resistance of diffuse large B-cell lymphoma by inhibiting ferroptosis via nf-κB/STAT3/GPX4 axis

Cancer Biology & Therapy, Год журнала: 2024, Номер 25(1)

Опубликована: Сен. 30, 2024

Drug resistance is a critical impediment to efficient therapy of diffuse large B-cell lymphoma (DLBCL) patients. Recent studies have highlighted the association between ferroptosis and drug that has been reported. Fatty acid synthase (FASN) always related poor prognosis. In this study, we investigate impact FASN on in DLBCL explore its potential modulation mechanisms. The clinical correlation mRNA expression was first analyzed confirm role based TCGA database. Next, investigated vitro vivo. Furthermore, combination RNA-seq, western blot, luciferase reporter, ChIP experiments employed elucidate underlying mechanism. prognosis for patients with worse when highly expressed, particularly those undergoing chemotherapy Adriamycin (ADM). promoted tumor growth ADM, both It noteworthy effect achieved by inhibiting ferroptosis, since Fer-1 (a inhibitor) treatment significantly recovered effects silencing while Erastin inducer) attenuated overexpressing FASN. Mechanistically, activated NF-κB/STAT3 signaling pathway through phosphorylating upstream IKKα IκBα, STAT3 GPX4 directly binding promoter. inhibits via NF-κB/STAT3/GPX4 pathway, indicating mediating ADM DLBCL.

Язык: Английский

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