Chemotherapy‐Induced Senescence Reprogramming Promotes Nasopharyngeal Carcinoma Metastasis by circRNA‐Mediated PKR Activation

Li, Qian; Zhao, Yuheng; Xu, Cheng; Liang, Ye‐Lin; Zhao, Yin; He, Qing‐Mei; Li, Junyan; Chen, Kailin; Han, Qiao; Liu, Na; Ma, Jun; Chen, Lei; Li, Ying‐Qin

doi:10.1002/advs.202205668

Cited by 9 publications

(9 citation statements)

References 62 publications

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“…CircWDR37, instead, exerts its role activating the PKR cascade, which results in the promotion of NF-κB activation, proliferation, and senescence-driven metastasis. In fact, experimentally lowered circWDR37 is correlated with chemotherapy response and favorable survival in nasopharyngeal carcinoma patients treated with gemcitabine or cisplatin [ 38 ]. Indeed, it could represent a possible therapeutic target.…”

Section: Discussionmentioning

confidence: 99%

Circular RNAs Could Encode Unique Proteins and Affect Cancer Pathways

Crudele

Bianchi

Terrazzan

et al. 2023

Biology

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circRNAs constitute a novel class of RNA, generally considered as non-coding RNAs; nonetheless, their coding potential has been under scrutiny. In this work, we systematically explored the predicted proteins of more than 160,000 circRNAs detected by exome capture RNA-sequencing and collected in the MiOncoCirc pan-cancer compendium, including normal and cancer samples from different types of tissues. For the functional evaluation, we compared their primary structure and domain composition with those derived from the same linear mRNAs. Among the 4362 circRNAs potentially encoding proteins with a unique primary structure and 1179 encoding proteins with a novel domain composition, 183 were differentially expressed in cancer. In particular, eight were associated with prognosis in acute myeloid leukemia. The functional classification of the dysregulated circRNA-encoded polypeptides showed an enrichment in the heme and cancer signaling, DNA-binding, and phosphorylation processes, and disclosed the roles of some circRNA-based effectors in cancer.

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Section: Discussionmentioning

confidence: 99%

Circular RNAs Could Encode Unique Proteins and Affect Cancer Pathways

Crudele

Bianchi

Terrazzan

et al. 2023

Biology

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“…Numerous studies have shown that circRNAs can participate in the progression of cancer by regulating the NF-κB pathway. 27,28 For example, circWDR37 deficiency inhibits chemotherapy-induced proliferation and metastasis of senescent NPC cells in vitro by inhibiting the NF-κB pathway. 27 We found that circRNA_CDKN1A acts by affecting the NF-κB pathway.…”

Section: Knockdown Of Circrna_cdkn1a Activates the Nf-κb Pathwaymentioning

confidence: 99%

“…27,28 For example, circWDR37 deficiency inhibits chemotherapy-induced proliferation and metastasis of senescent NPC cells in vitro by inhibiting the NF-κB pathway. 27 We found that circRNA_CDKN1A acts by affecting the NF-κB pathway. However, this study only preliminarily confirmed the correlation between circRNA_CDKN1A and the NF-κB pathway, as no target gene directly regulated by circRNA_CDKN1A was found.…”

Section: Knockdown Of Circrna_cdkn1a Activates the Nf-κb Pathwaymentioning

confidence: 99%

Downregulated circRNA_CDKN1A promotes gallbladder cancer progression through activation of the NF‐κB pathway

Hu,

Yang,

Wang

et al. 2024

Cell Biochemistry & Function

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This study uncovered the potential clinical value and molecular driving mechanisms of circular RNAs (circRNAs) in gallbladder cancer (GBC). Differentially expressed circRNAs in GBC cells were screened by high‐throughput sequencing. CircRNA_CDKN1A (circBase ID: hsa_circ_0076194) was knocked out in BGC‐SD cells through transfection with sh‐circRNA_CDKN1A. Then, proliferation was investigated via CCK8 and EdU assays, apoptosis via flow cytometry, migration via wound healing assays, and invasion via Transwell assays. Bioinformatics analysis of circRNA_CDKN1A‐related signaling pathways was performed using MetScape and g:Profiler. Results showed that the knockdown of circRNA_CDKN1A enhanced the proliferation, migration, and invasion of GBC cells and inhibited apoptosis. In addition, knocking out circRNA_CDKN1A promoted GBC cell proliferation and enhanced the dry indices of the OCT4 protein and CD34 expression levels. The knockdown of circRNA_CDKN1A activated the epithelial–mesenchymal transition pathway. Bioinformatics analysis revealed that the biological role of circRNA_CDKN1A in GBC cells involved the NF‐κB pathway. LY2409881, which is an NF‐κB inhibitor, reversed the effects induced by the knockdown of circRNA_CDKN1A in GBC‐SD cells. In summary, the knockdown of circRNA_CDKN1A promoted the progression of GBC by activating the NF‐κB signaling pathway. For the first time, this study revealed the mechanism of circRNA_CDKN1A‐mediated regulatory action in GBC and identified the newly discovered circRNA_CDKN1A–NF‐κB signaling axis as a potentially important candidate for clinical therapy and prognostic diagnosis of GBC.

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“…NF-κB is an important transcription factor that promotes inflammatory responses and immune responses, and is also involved in the regulation of apoptosis and senescence. 107, 136 Guo et al 121 demonstrated that circARHGEF28 could negatively regulate the NF-κB pathway by sponging miR-671-5p. Another study proved that circRNF10 inhibited the activation of NF-κB signaling pathway by interacting with DEAH (Asp-Glu-Ala-His) box helicase 15 (DHX15).…”

Section: Nf-κb Signaling Pathwaymentioning

confidence: 99%

“…NF‐κB is an important transcription factor that promotes inflammatory responses and immune responses, and is also involved in the regulation of apoptosis and senescence 107,136 …”

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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Chemotherapy‐Induced Senescence Reprogramming Promotes Nasopharyngeal Carcinoma Metastasis by circRNA‐Mediated PKR Activation

Cited by 9 publications

References 62 publications

Circular RNAs Could Encode Unique Proteins and Affect Cancer Pathways

Circular RNAs Could Encode Unique Proteins and Affect Cancer Pathways

Downregulated circRNA_CDKN1A promotes gallbladder cancer progression through activation of the NF‐κB pathway

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

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