Cadmium induces ferroptosis and apoptosis by modulating <scp>miR</scp>‐34a‐5p/Sirt1axis in <scp>PC12</scp> cells

Hao, Rili; Ge, Junlin; Song, Xubin; Li, Feng; Sun‐Waterhouse, Dongxiao

doi:10.1002/tox.23376

Cited by 44 publications

(28 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mir-34a-5p expression is significantly increased in the synovium of patients with advanced OA, but the underlying mechanisms need to be further elucidated ( Endisha et al, 2021 ). Recent research has found that mir-34a-5p targeting SIRT1 induces cell ferroptosis ( Hao et al, 2022 ). But its role in OA is still unclear.…”

Section: Discussionmentioning

confidence: 99%

Identification and verification of ferroptosis-related genes in the synovial tissue of osteoarthritis using bioinformatics analysis

Xia

Gong

2022

Front. Mol. Biosci.

View full text Add to dashboard Cite

Background: Osteoarthritis (OA) is a major factor causing pain and disability. Studies performed to date have suggested that synovitis is possibly a critical OA-related pathological change. Ferroptosis represents a novel type of lipid peroxidation-induced iron-dependent cell death. However, its effect on OA remains largely unclear.Objective: This work focused on identifying and validating the possible ferroptosis-related genes (FRGs) involved in synovitis of OA through bioinformatics analysis.Materials and Methods: The microarray dataset GSE55235 was downloaded in the database Gene Expression Omnibus (GEO). By the Venn diagram and GEO2R, differentially expressed genes (DEGs) and ferroptosis DEGs (FDEGs) were detected. DEGs were screened by GO and KEGG enrichment analysis, as well as protein-protein interaction (PPI) analysis. Besides, the software Cytoscape and database STRING were utilized to construct hub gene networks. Moreover, this study used the database NetworkAnalyst to predict the target miRNAs of the hub genes. Finally, the hub genes were confirmed by analysis of the receiver operating characteristic (ROC) curve on the GSE12021 and GSE1919 databases. Considering the relationship between ferroptosis and immunity, this study applied CIBERSORTx to analyze the immune infiltration in OA in addition.Results: This work discovered seven genes, including ATF3, IL6, CDKN1A, IL1B, EGR1, JUN, and CD44, as the hub FDEGs. The ROC analysis demonstrated that almost all hub genes had good diagnostic properties in GSE12021 and GSE 1919.Conclusion: This study discovered seven FDEGs to be the possible diagnostic biomarkers and therapeutic targets of synovitis during OA, which sheds more light on the pathogenesis of OA at the transcriptome level.

show abstract

Section: Discussionmentioning

confidence: 99%

Identification and verification of ferroptosis-related genes in the synovial tissue of osteoarthritis using bioinformatics analysis

Xia

Gong

2022

Front. Mol. Biosci.

View full text Add to dashboard Cite

show abstract

“…The mechanistic study indicated that Cd exposure induced miR-34a-5p expression, and up-regulated miR-34a-5p contributed to Cd-induced apoptosis and ferroptosis, likely through directly targeting sirtuin 1 (Sirt1), as the down-regulation of miR-34a-5p mitigated the apoptosis and ferroptosis caused by Cd. However, the role of down-regulated Sirt1 in miR-34a-5p-mediated apoptosis and ferroptosis was not validated in this study [ 199 ]. In BEAS-2B and BEP2D lung epithelial cells, Cd exposure resulted in the down-regulation of miR-30e, causing up-regulated expression of snail family transcriptional repressor 1 (SNAIL1), a direct target of miR-30e, and resultant EMT induction.…”

Section: Cadmium (Cd)mentioning

confidence: 96%

Epigenetic Regulation in Chromium-, Nickel- and Cadmium-Induced Carcinogenesis

Zhao

Islam

Wang

et al. 2022

Cancers

View full text Add to dashboard Cite

Environmental and occupational exposure to heavy metals, such as hexavalent chromium, nickel, and cadmium, are major health concerns worldwide. Some heavy metals are well-documented human carcinogens. Multiple mechanisms, including DNA damage, dysregulated gene expression, and aberrant cancer-related signaling, have been shown to contribute to metal-induced carcinogenesis. However, the molecular mechanisms accounting for heavy metal-induced carcinogenesis and angiogenesis are still not fully understood. In recent years, an increasing number of studies have indicated that in addition to genotoxicity and genetic mutations, epigenetic mechanisms play critical roles in metal-induced cancers. Epigenetics refers to the reversible modification of genomes without changing DNA sequences; epigenetic modifications generally involve DNA methylation, histone modification, chromatin remodeling, and non-coding RNAs. Epigenetic regulation is essential for maintaining normal gene expression patterns; the disruption of epigenetic modifications may lead to altered cellular function and even malignant transformation. Therefore, aberrant epigenetic modifications are widely involved in metal-induced cancer formation, development, and angiogenesis. Notably, the role of epigenetic mechanisms in heavy metal-induced carcinogenesis and angiogenesis remains largely unknown, and further studies are urgently required. In this review, we highlight the current advances in understanding the roles of epigenetic mechanisms in heavy metal-induced carcinogenesis, cancer progression, and angiogenesis.

show abstract

“…In duck brains, a study found that cadmium and molybdenum co-induced pyroptosis by inhibiting the Nrf2-mediated antioxidant defense response [ 130 ]. In a recent report, cadmium (2 and 4 μM) induced ferroptosis and apoptosis in PC12 cells by regulating the miR-34a-5p/Sirt1 axis [ 131 ]. In a cadmium induction experiment in swine, cadmium exposure induced ferroptosis pathways by activating oxidative stress, eventually causing cerebrum and cerebellum damage [ 132 ].…”

Section: The Toxicity Of Cadmium Toward the Kidney Liver Bone And Brainmentioning

confidence: 99%

The Effect of Oxidative Stress-Induced Autophagy by Cadmium Exposure in Kidney, Liver, and Bone Damage, and Neurotoxicity

Yue

et al. 2022

IJMS

View full text Add to dashboard Cite

Environmental and occupational exposure to cadmium has been shown to induce kidney damage, liver injury, neurodegenerative disease, and osteoporosis. However, the mechanism by which cadmium induces autophagy in these diseases remains unclear. Studies have shown that cadmium is an effective inducer of oxidative stress, DNA damage, ER stress, and autophagy, which are thought to be adaptive stress responses that allow cells exposed to cadmium to survive in an adverse environment. However, excessive stress will cause tissue damage by inducing apoptosis, pyroptosis, and ferroptosis. Evidently, oxidative stress-induced autophagy plays different roles in low- or high-dose cadmium exposure-induced cell damage, either causing apoptosis, pyroptosis, and ferroptosis or inducing cell survival. Meanwhile, different cell types have different sensitivities to cadmium, which ultimately determines the fate of the cell. In this review, we provided a detailed survey of the current literature on autophagy in cadmium-induced tissue damage. A better understanding of the complex regulation of cell death by autophagy might contribute to the development of novel preventive and therapeutic strategies to treat acute and chronic cadmium toxicity.

show abstract

Cadmium induces ferroptosis and apoptosis by modulating miR‐34a‐5p/Sirt1axis in PC12 cells

Cited by 44 publications

References 41 publications

Identification and verification of ferroptosis-related genes in the synovial tissue of osteoarthritis using bioinformatics analysis

Identification and verification of ferroptosis-related genes in the synovial tissue of osteoarthritis using bioinformatics analysis

Epigenetic Regulation in Chromium-, Nickel- and Cadmium-Induced Carcinogenesis

The Effect of Oxidative Stress-Induced Autophagy by Cadmium Exposure in Kidney, Liver, and Bone Damage, and Neurotoxicity

Contact Info

Product

Resources

About