The interplay of miRNAs and ferroptosis in diseases related to iron overload

Jin, Shikai; Liu, Pu-Ste; Zheng, Daheng; Xie, Xin

doi:10.1007/s10495-023-01890-w

Cited by 12 publications

(4 citation statements)

References 196 publications

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“…Morphologically, ferroptosis is primarily distinguished by substantial mitochondrial shrinkage accompanied by heightened membrane density, along with a reduction or disappearance of mitochondrial cristae. Recent research has demonstrated the important regulatory function ferroptosis plays in the development and course of a number of diseases, such as cancer, ischemia-reperfusion injury, and neurodegenerative disorders (Jin et al 2023; (Xie et al 2016). Therefore, ferroptosis-related genes (FRGs) have the potential to serve as prognostic biomarkers in LUAD, effectively predicting the overall survival of LUAD patients (Zhang et al 2021a).…”

Section: Introductionmentioning

confidence: 99%

Biomarkers Exploration of Epithelial-Mesenchymal Transition and Ferroptosis in Lung Adenocarcinoma: Transcriptomic Analysis and Mendelian Randomization

Zhang,

Hou,

Chen

et al. 2024

Preprint

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Background:Studies have demonstrated the prognostic potential of Epithelial-mesenchymal transition (EMT)-related genes (ERGs) and ferroptosis-related genes (FRGs) for Lung adenocarcinoma (LUAD) patients, but their correlation and underlying molecular mechanisms remain unknown. Thus, this investigation employs transcriptomics, Mendelian randomization (MR) analysis and single-cell data to explore the relationship and prognosis of EMT and ferroptosis with LUAD. Methods:Transcriptomic data from training and validation sets, along with single-cell datasets, were utilized. Prognostic-related differentially expressed (DE)-FRGs and DE-ERGs were identified, and a risk model was constructed using MR analysis and machine learning techniques. Single-cell data were analyzed to characterize model genes’ expression and function. Results:Totally, 40 DE-FRGs and 222 DE-ERGs related to prognostic were identified in TCGA-LUAD. And there were 7 candidate genes by MR analysis. A total of 6 model genes (TFAM, ALOX15, GATA1, ALAD, PDCD4 and NDRG2) were selected to construct a risk model and the model was verified by GSE11969. Meanwhile, stage, N, T, and risk score were screened out as independent prognostic factors via univariate and multivariate cox regression and scores were counted to build a nomogram. Then, MR analysis results revealed that 6 model genes were significantly causally associated with LUAD. Meanwhile, model genes were mainly enriched in NK cells, T cells, Endothelial cell clusters, etc. by single-cell analysis. Conclusion:TFAM, ALOX15, GATA1, ALAD, PDCD4 and NDRG2 played crucial roles in LUAD prognosis, providing refresh directions for the treatment of LUAD.

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Section: Introductionmentioning

confidence: 99%

Biomarkers Exploration of Epithelial-Mesenchymal Transition and Ferroptosis in Lung Adenocarcinoma: Transcriptomic Analysis and Mendelian Randomization

Zhang,

Hou,

Chen

et al. 2024

Preprint

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“…The regulatory mechanisms of ferroptosis involve oxidation system and antioxidant system, including iron metabolism, lipid metabolism, glutathione-GPX4 pathway, and glutamate/cystine transport [ 13 ]. An increasing body of evidence reveals the critical role of miRNAs in ferroptosis by targeting various ferroptosis players mentioned above [ 14 ]. Meanwhile, miRNAs can post-transcriptionally regulate the expression of genes related to iron acquisition, export, storage, utilization, and regulation of systemic iron homeostasis [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Ferroptosis Altered microRNAs Expression in HT-1080 Fibrosarcoma Cells Based on Small RNA Sequencing and Bioinformatics Analysis

Zhang,

Wang,

Ding

et al. 2024

Nutrients

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Iron is an essential trace element in the human body. However, excess iron is harmful and may cause ferroptosis. The expression and role of microRNAs (miRNAs) in ferroptosis remain largely unknown. A model of ferroptosis induced by ferric ammonium citrate in HT-1080 cells was established in this study. The miRNAs expression profiles of the control and iron groups were obtained using small RNA sequencing and verified using qRT-PCR. A total of 1346 known miRNAs and 80 novel miRNAs were identified, including 12 up-regulated differentially expressed miRNAs (DE-miRNAs) and 16 down-regulated DE-miRNAs. SP1 was the most important upstream transcription factor regulating DE-miRNAs. The downstream target genes of DE-miRNAs were predicted based on miRDB, TargetScan, and miRBase databases, and 403 common target genes were screened. GO annotation and KEGG analysis revealed that the target genes were mainly involved in various biological processes and regulatory pathways, especially the MAPK signaling pathway and PI3K-Akt signaling pathway. Afterwards, a target genes network was constructed using STRING and Cytoscape, and the hub genes were compared with the ferroptosis database (FerrDb V2) to discover the hub genes related to ferroptosis. EGFR, GSK3B, PARP1, VCP, and SNCA were screened out. Furthermore, a DE-miRNAs-target genes network was constructed to explore key DE-miRNAs. hsa-miR-200c-3p, hsa-miR-26b-5p, and hsa-miR-7-5p were filtered out. Comprehensive bioinformatics analysis of miRNAs and its upstream and downstream regulation in ferroptosis in HT-1080 cells using small RNA sequencing is helpful for understanding the role of miRNAs in iron overload-related diseases and ferroptosis-targeted therapy for cancer.

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“…Furthermore, miR-96 and miR-183 played crucial roles in synaptic transmission in the auditory brainstem [ 26 ]. MiRNAs also play a regulatory role in ferroptosis, and studies have shown that the miRNA/GPX4 pathway regulates GPX4 expression in cells undergoing ferroptosis in various diseases [ 27 ]. Additionally, miRNAs have been implicated in sevoflurane-induced ferroptosis-related neurotoxicity [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

The miR-182-5p/GPX4 Pathway Contributes to Sevoflurane-Induced Ototoxicity via Ferroptosis

Jin,

Yu,

Zhou

et al. 2024

IJMS

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Our study aimed to investigate the role of ferroptosis in sevoflurane-induced hearing impairment and explore the mechanism of the microRNA-182-5p (miR-182-5p)/Glutathione Peroxidase 4 (GPX4) pathway in sevoflurane-induced ototoxicity. Immunofluorescence staining was performed using myosin 7a and CtBP2. Cell viability was assessed using the CCK-8 kit. Fe2+ concentration was measured using FerroOrange and Mi-to-FerroGreen fluorescent probes. The lipid peroxide level was assessed using BODIPY 581/591 C11 and MitoSOX fluorescent probes. The auditory brainstem response (ABR) test was conducted to evaluate the hearing status. Bioinformatics tools and dual luciferase gene reporter analysis were used to confirm the direct targeting of miR-182-5p on GPX4 mRNA. GPX4 and miR-182-5p expression in cells was assessed by qRT-PCR and Western blot. Ferrostatin-1 (Fer-1) pretreatment significantly improved hearing impairment and damage to ribbon synapses in mice caused by sevoflurane exposure. Immunofluorescence staining revealed that Fer-1 pretreatment reduced intracellular and mitochondrial iron overload, as well as lipid peroxide accumulation. Our findings indicated that miR-182-5p was upregulated in sevoflurane-exposed HEI-OC1 cells, and miR-182-5p regulated GPX4 expression by binding to the 3′UTR of GPX4 mRNA. The inhibition of miR-182-5p attenuated sevoflurane-induced iron overload and lipid peroxide accumulation. Our study elucidated that the miR-182-5p/GPX4 pathway was implicated in sevoflurane-induced ototoxicity by promoting ferroptosis.

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The interplay of miRNAs and ferroptosis in diseases related to iron overload

Cited by 12 publications

References 196 publications

Biomarkers Exploration of Epithelial-Mesenchymal Transition and Ferroptosis in Lung Adenocarcinoma: Transcriptomic Analysis and Mendelian Randomization

Biomarkers Exploration of Epithelial-Mesenchymal Transition and Ferroptosis in Lung Adenocarcinoma: Transcriptomic Analysis and Mendelian Randomization

Ferroptosis Altered microRNAs Expression in HT-1080 Fibrosarcoma Cells Based on Small RNA Sequencing and Bioinformatics Analysis

The miR-182-5p/GPX4 Pathway Contributes to Sevoflurane-Induced Ototoxicity via Ferroptosis

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