HCP5 Derived Novel Microprotein Triggers Progression of Gastric Cancer through Regulating Ferroptosis DOI Creative Commons
Qiuhui Li, Guoqing Guo, Yuli Chen

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 24, 2024

Abstract The context of long noncoding RNAs (lncRNAs) contains many unannotated open reading frames (ORFs). These ORFs potentially encode novel proteins or peptides with crucial roles in various human cancers, yet the translational potential these lncRNAs and functions protein products remain largely unexplored, especially gastric cancer (GC). In this study, a comprehensive analysis is performed identified GC associated lncRNA known as HCP5, which non‐canonical ORF. Further showed that HCP5‐132aa, microprotein encoded by HCP5 harboring ORF, highly expressed cells tissues, can promote proliferation inhibiting ferroptosis. Mechanistically, HCP5‐132aa enhances interaction between YBX1 ELAVL1, facilitates recognition at m 5 C site 3′UTR SLC7A11 G6PD mRNA, preserves their stability via ELAVL1. By employing Cas9/sgRNA delivery system AAV vivo, effectively knocked out inhibition tumor growth patient‐derived xenograft model are achieved. findings demonstrate derived from mediates repression ferroptosis, thereby driving progression identifying new therapeutic target for its treatment.

Language: Английский

Ferroptosis in cancer: From molecular mechanisms to therapeutic strategies DOI Creative Commons
Qian Zhou,

Yu Meng,

Daishi Li

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: March 8, 2024

Ferroptosis is a non-apoptotic form of regulated cell death characterized by the lethal accumulation iron-dependent membrane-localized lipid peroxides. It acts as an innate tumor suppressor mechanism and participates in biological processes tumors. Intriguingly, mesenchymal dedifferentiated cancer cells, which are usually resistant to apoptosis traditional therapies, exquisitely vulnerable ferroptosis, further underscoring its potential treatment approach for cancers, especially refractory cancers. However, impact ferroptosis on extends beyond direct cytotoxic effect cells. induction not only inhibits but also promotes development due negative anticancer immunity. Thus, comprehensive understanding role crucial successful translation therapy from laboratory clinical applications. In this review, we provide overview recent advancements cancer, covering molecular mechanisms, functions, regulatory pathways, interactions with microenvironment. We summarize applications immunotherapy, radiotherapy, systemic therapy, well inhibition various conditions. finally discuss markers, current challenges future directions cancer.

Language: Английский

Citations

153
7-Dehydrocholesterol is an endogenous suppressor of ferroptosis DOI
Florêncio Porto Freitas, Hamed Alborzinia, Ancély Ferreira dos Santos

et al.

Nature, Journal Year: 2024, Volume and Issue: 626(7998), P. 401 - 410

Published: Jan. 31, 2024

Language: Английский

Citations

122
Drug-tolerant persister cells in cancer: the cutting edges and future directions DOI
Yi Pu, Lu Li, Haoning Peng

et al.

Nature Reviews Clinical Oncology, Journal Year: 2023, Volume and Issue: 20(11), P. 799 - 813

Published: Sept. 25, 2023

Language: Английский

Citations

62
The mechanisms of ferroptosis and its role in atherosclerosis DOI Open Access

Xi Xu,

Xiaodan Xu, Mengqing Ma

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 171, P. 116112 - 116112

Published: Jan. 2, 2024

Ferroptosis is a newly identified form of non-apoptotic programmed cell death, characterized by the iron-dependent accumulation lethal lipid reactive oxygen species (ROS) and peroxidation membrane polyunsaturated fatty acid phospholipids (PUFA-PLs). unique among other death modalities in many aspects. It initiated excessive oxidative damage due to iron overload compromised antioxidant defense systems, including system Xc-/ glutathione (GSH)/glutathione peroxidase 4 (GPX4) pathway GPX4-independent pathways. In past ten years, ferroptosis was reported play critical role pathogenesis various cardiovascular diseases, e.g., atherosclerosis (AS), arrhythmia, heart failure, diabetic cardiomyopathy, myocardial ischemia-reperfusion injury. Studies have dysfunctional metabolism abnormal expression profiles ferroptosis-related factors, iron, GSH, GPX4, ferroportin (FPN), SLC7A11 (xCT), as indicators for atherogenesis. Moreover, plaque cells, i.e., vascular endothelial (VEC), macrophage, smooth muscle (VSMC), positively correlate with atherosclerotic development. Many macromolecules, drugs, Chinese herbs, food extracts can inhibit atherogenic process suppressing cells. contrast, some inducers significant pro-atherogenic effects. However, mechanisms through which affects progression AS still need be well-known. This review summarizes molecular their emerging AS, aimed at providing novel, promising druggable targets anti-AS therapy.

Language: Английский

Citations

41
5-Methylcytosine transferase NSUN2 drives NRF2-mediated ferroptosis resistance in non-small cell lung cancer DOI Creative Commons
Youming Chen,

Zuli Jiang,

Chenxing Zhang

et al.

Journal of Biological Chemistry, Journal Year: 2024, Volume and Issue: 300(4), P. 106793 - 106793

Published: Feb. 24, 2024

RNA 5-methylcytosine (m5C) is an abundant chemical modification in mammalian RNAs and plays crucial roles regulating vital physiological pathological processes, especially cancer. However, the dysregulation of m5C its underlying mechanisms non-small cell lung cancer (NSCLC) remain unclear. Here we identified that NSUN2, a key methyltransferase, highly expressed NSCLC tumor tissue. We found elevated NSUN2 expression levels strongly correlate with grade size, predicting poor outcomes for patients. Furthermore, RNA-seq subsequent confirmation studies revealed antioxidant-promoting transcription factor NRF2 target depleting decreases increases sensitivity cells to ferroptosis activators both vitro vivo. Intriguingly, methylated-RIP-qPCR assay results indicated mRNA has higher level when overexpressed but shows no significant changes methyltransferase-deficient group. Mechanistically, confirmed upregulates by enhancing stability through within 5'UTR region recognized specific reader protein YBX1, rather than influencing translation. In rescue experiments, show knocking down diminished proliferation, migration, tolerance mediated overexpression. conclusion, our study unveils novel regulatory mechanism which sustains m5C-YBX1-axis, suggesting targeting regulated pathway might offer promising therapeutic strategies

Language: Английский

Citations

18
Bone-targeting exosome nanoparticles activate Keap1 / Nrf2 / GPX4 signaling pathway to induce ferroptosis in osteosarcoma cells DOI Creative Commons
Wenkai Chen,

Zongguang Li,

Naichun Yu

et al.

Journal of Nanobiotechnology, Journal Year: 2023, Volume and Issue: 21(1)

Published: Sept. 30, 2023

In recent years, the development of BMSCs-derived exosomes (EXO) for treatment osteosarcoma (OS) is a safe and promising modality OS treatment, which can effectively deliver drugs to tumor cells in vivo. However, differences carried, binding EXOs other organs limit their therapeutic efficacy. Therefore, improving OS-targeting ability BMSCs developing new crucial clinical application targeted therapy OS.In this study, we constructed potential nano platform by modifying using bone-targeting peptide SDSSD encapsulated capreomycin (CAP) within shell. These nanoparticles (NPs) showed homologous targeting (BT-EXO) significantly promotes cellular endocytosis vitro accumulation Furthermore, our results revealed that NPs induced ferroptosis prompting excessive reactive oxygen species (ROS), Fe2+ aggregation, lipid peroxidation further identified anticancer molecular mechanism as transduced Keap1/Nrf2/GPX4 signaling pathway. Also, these NP-directed significant inhibition growth vivo with no side effects.These suggest have superior activity mouse models vivo, providing strategy combining ferroptosis-based chemotherapy OS.

Language: Английский

Citations

24
YTHDC1 as a tumor progression suppressor through modulating FSP1-dependent ferroptosis suppression in lung cancer DOI
Shuai Yuan,

Shu Xi,

Hong Weng

et al.

Cell Death and Differentiation, Journal Year: 2023, Volume and Issue: 30(12), P. 2477 - 2490

Published: Oct. 30, 2023

Language: Английский

Citations

23
Epigenetic modification of ferroptosis by non-coding RNAs in cancer drug resistance DOI Creative Commons
Hongquan Wang, Joshua S. Fleishman,

Sihang Cheng

et al.

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

Published: Aug. 27, 2024

Abstract The development of drug resistance remains a major challenge in cancer treatment. Ferroptosis, unique type regulated cell death, plays pivotal role inhibiting tumour growth, presenting new opportunities treating chemotherapeutic resistance. Accumulating studies indicate that epigenetic modifications by non-coding RNAs (ncRNA) can determine vulnerability to ferroptosis. In this review, we first summarize the growth/development. Then, core molecular mechanisms ferroptosis, its upstream regulation, and downstream effects on Finally, review recent advances understanding how ncRNAs regulate ferroptosis from such modulate This aims enhance general ncRNA-mediated regulatory which highlighting ncRNA-ferroptosis axis as key druggable target overcoming

Language: Английский

Citations

15
Emerging roles of mitochondrial functions and epigenetic changes in the modulation of stem cell fate DOI Open Access
Chen‐Song Zhang, Yang Meng, Junhong Han

et al.

Cellular and Molecular Life Sciences, Journal Year: 2024, Volume and Issue: 81(1)

Published: Jan. 12, 2024

Language: Английский

Citations

13
Iron toxicity, ferroptosis and microbiota in Parkinson’s disease: Implications for novel targets DOI
Fernanda V. Carvalho,

Harold E. Landis,

Bruk Getachew

et al.

Advances in neurotoxicology, Journal Year: 2024, Volume and Issue: unknown, P. 105 - 132

Published: Jan. 1, 2024

Language: Английский

Citations

9