N6-methyladenosine hypomethylation of circGPATCH2L regulates DNA damage and apoptosis through TRIM28 in intervertebral disc degeneration

Song, Jian; Xie, Lin; Xu, Guangyu; Zheng, Chaojun; Xia, Xinlei; Lu, Feizhou; Ma, Xiaosheng; Zou, Fei; Jiang, Jianyuan; Wang, Hongli

doi:10.1038/s41418-023-01190-5

Cited by 17 publications

(3 citation statements)

References 69 publications

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“…Chen et al ( Chen et al, 2023 ) innovatively explored the mechanism and role of m6A methylation in IDD to regulate circ GPATCH2L . They screened and verified that circ GPATCH2L expression is upregulated in IDD, and m6A methylation is significantly reduced.…”

Section: Detrimental Genes In Ivdmentioning

confidence: 99%

“…circRNAs bind to miRNAs and affect the expression of their target genes. Notably, a preliminary study by Chen et al ( Chen et al, 2023 ) found that circ GPATCH2L directly binds to target proteins and influences the development of IDD, an area that deserves further research. Current research on circRNAs has revealed that they can accelerate disc degeneration and act as protective factors that slow the progression of IDD.…”

Section: Potential Clinical Applications Of Circrnasmentioning

confidence: 99%

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Circular RNA and intervertebral disc degeneration: unravelling mechanisms and implications

Xie,

Wu,

et al. 2023

Front. Mol. Biosci.

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Low back pain (LBP) is a major public health problem worldwide and a significant health and economic burden. Intervertebral disc degeneration (IDD) is the reason for LBP. However, we have not identified effective therapeutic strategies to address this challenge. With accumulating knowledge on the role of circular RNAs in the pathogenesis of IDD, we realised that circular RNAs (circRNAs) may have tremendous therapeutic potential and clinical application prospects in this field. This review presents an overview of the current understanding of characteristics, classification, biogenesis, and function of circRNAs and summarises the protective and detrimental circRNAs involved in the intervertebral disc that have been studied thus far. This review is aimed to help researchers better understand the regulatory role of circRNAs in the progression of IDD, reveal their clinical therapeutic potential, and provide a theoretical basis for the prevention and targeted treatment of IDD.

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Section: Detrimental Genes In Ivdmentioning

confidence: 99%

Section: Potential Clinical Applications Of Circrnasmentioning

confidence: 99%

Circular RNA and intervertebral disc degeneration: unravelling mechanisms and implications

Xie,

Wu,

et al. 2023

Front. Mol. Biosci.

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“…p21 is the downstream activation molecule of p53, a cell cycle protein that has the effect of blocking cell cycle operation. This signaling pathway is a response mainly caused by cellular DNA damage 5,90,92,130–133 …”

Section: Circular Rnas Regulate Cellular Senescence Via Various Pathwaysmentioning

confidence: 99%

Cellular senescence: A potential mode of circular RNAs regulating prostate cancer

Li,

Fan,

Zhang

et al. 2023

MedComm – Oncology

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Cellular senescence is a state characterized by permanent cell cycle stoppage, which has long been viewed as a protective mechanism against neoplasia. However, accumulating evidence reveal that cellular senescence variously stimulates tumorigenesis and malignant progression in certain contexts. Senescence‐associated secretory phenotype (SASP) is a crucial feature of senescent cells and the main way they function. Prostate cancer (PCa) is apparently an age‐related tumor with a high prevalence in the elderly. With the aggravation of population aging the morbidity of PCa continues to rise. And with the progress of the disease, most patients eventually develop castration‐resistant PCa (CRPC) or drug resistance, which poses a challenge for the treatment of PCa and aggravates the burden on patients and society. Circular RNAs (circRNAs) are a class of endogenous noncoding RNAs formed by back‐splicing of pre‐mRNAs. Characterized by special covalently closed circular structure, they play important regulatory roles in various tumors. Numerous studies have revealed that circRNAs can regulate PCa and cellular senescence in diverse ways. This review explores a potential mode that circRNAs regulate PCa, reveales a significant mechanism of tumorigenesis and progression for PCa, suggesting a new strategy for PCa research.

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Cartilage Endplate‐Targeted Engineered Exosome Releasing and Acid Neutralizing Hydrogel Reverses Intervertebral Disc Degeneration

Zhan,

Cui,

Zhang

et al. 2024

Adv Healthcare Materials

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Cartilage endplate cell (CEPC) and nucleus pulposus cell (NPC) inflammation are critical factors that contribute to intervertebral disc degeneration (IVDD). Recent evidence indicated that iron ion influx, reactive oxygen species (ROS), and the cGAS‐STING pathway are involved in CEPC inflammatory degeneration. Moreover, cytokines produced by degenerating CEPCs and lactic acid accumulation within the microenvironment significantly contribute to NPC inflammation. Consequently, simultaneous alleviation of CEPC inflammation and correction of the acidic microenvironment are anticipated to reverse IVDD. Herein, CEPC‐targeted engineered exosomes loaded with salvianolic acid A are incorporated into a CaCO3/chitosan hydrogel, forming a composite gel, CAP‐sEXOs@Gel. Notably, CAP‐sEXOs@Gel shows long local retention, realizes the slow release of CAP‐sEXOs and specific uptake by CEPCs. After uptake by CEPCs, CAP‐sEXOs reduce intracellular iron ion and ROS by inhibiting hypoxia‐inducible factor‐2α (HIF‐2α)/TfR1 expression. Iron ion influx and ROS inhibition contribute to the maintenance of normal mitochondrial function and reduced mtDNA leakage, suppresing the cGAS‐STING pathway. Additionally, the CaCO3 component of CAP‐sEXOs@Gel neutralizes H+, thereby alleviating NPC inflammation. Collectively, this novel composite hydrogel demonstrates the ability to concurrently inhibit CEPC and NPC inflammation, thereby presenting a promising therapeutic approach for IVDD.

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N6-methyladenosine hypomethylation of circGPATCH2L regulates DNA damage and apoptosis through TRIM28 in intervertebral disc degeneration

Cited by 17 publications

References 69 publications

Circular RNA and intervertebral disc degeneration: unravelling mechanisms and implications

Circular RNA and intervertebral disc degeneration: unravelling mechanisms and implications

Cellular senescence: A potential mode of circular RNAs regulating prostate cancer

Cartilage Endplate‐Targeted Engineered Exosome Releasing and Acid Neutralizing Hydrogel Reverses Intervertebral Disc Degeneration

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