Circular RNA circPBX3 promotes cisplatin resistance of ovarian cancer cells via interacting with IGF2BP2 to stabilize ATP7A mRNA expression

Fu, Lihua; Zhang, Dan; Yi, Nuo; Cao, Ye; Wei, Yaxian; Wang, Wenjing; Li, Li

doi:10.1007/s13577-022-00748-8

Cited by 15 publications

(13 citation statements)

References 38 publications

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“…It has been reported that IGF2BP2 has a significant effect on the regulation of the proliferation of SK-OV-3 and A2780 cells 26 and the chemoresistance of OC. 27 High expression of IGF2BP2 is related to unfavorable survival of OC patients. 28 This study demonstrated a remarkably high-expression level of IGF2BP2 in OC cells/tissues compared with non-tumorous ovarian epithelial cells/normal ovarian tissues, respectively, but was low in chemoresistant cells compared with chemosensitive cells.…”

Section: Discussionmentioning

confidence: 99%

Insulin-like growth factor 2 mRNA-binding protein 2 is a therapeutic target in ovarian cancer

Yuan,

Li,

Wang

et al. 2023

Exp Biol Med (Maywood)

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Ovarian cancer (OC) is a fatal gynecologic disease. The most common treatment for OC patients is surgery combined with chemotherapy but most patients at advanced stages eventually develop relapse due to chemoresistance. This study examined the role and function of insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) in OC. We observed that the expression of IGF2BP2 mRNA and protein was up-regulated in OC cells and tissues using quantitative real-time polymerase chain reaction (qRT-PCR) and western blot, respectively. An increase in IGF2BP2 expression at mRNA and protein levels was verified by the analyses of The Cancer Genome Atlas (TCGA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC), respectively. Gene Expression Omnibus (GEO) and Cancer Cell Line Encyclopedia (CCLE) databases were applied to analyze the expression and clinical value of IGF2BP2. Gene set enrichment analysis (GSEA), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Ontology (GO) analyses explored biological functions and the involvement of IGF2BP2 in cell growth. Indeed, the knockdown of IGF2BP2 resulted in the inhibition of OC cell proliferation evaluated by the Cell Counting Kit-8 assay. Genomic amplification of IGF2BP2 partly accounted for its overexpression. High expression of IGF2BP2 was associated with signal transducer and activator of transcription 1 (STAT1) and drug sensitivity and was correlated with an unfavorable survival outcome in OC patients. Furthermore, the responsiveness of chemotherapy and immunotherapy were analyzed using the “pRRophetic” R package and The Cancer Immune Atlas (TCIA) database, respectively. The low expression of IGF2BP2 was associated with chemoresistance but with high tumor microenvironment scores and tumor-infiltrating immune cells, suggesting that immunotherapy may apply in chemoresistant patients. The alteration of IGF2BP2 expression may respond to chemotherapy and immunotherapy. Thus, IGF2BP2 shows potential as a therapeutic target and diagnostic biomarker for OC.

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Section: Discussionmentioning

confidence: 99%

Insulin-like growth factor 2 mRNA-binding protein 2 is a therapeutic target in ovarian cancer

Yuan,

Li,

Wang

et al. 2023

Exp Biol Med (Maywood)

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“…ATP7A is upregulated in gemcitabine-resistant non-small cell lung cancer ( 40 ). In esophageal and ovarian cancers, ATP7A is associated with cisplatin resistance ( 41 – 43 ). Our study demonstrated for the first time that ATP7A is upregulated in CCA; however, whether it promotes CCA progression needs to be confirmed by further studies.…”

Section: Discussionmentioning

confidence: 99%

Establishment and experimental validation of a novel cuproptosis-related gene signature for prognostic implication in cholangiocarcinoma

Chen

Tong

et al. 2022

Front. Oncol.

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BackgroundCholangiocarcinoma (CCA) is a highly malignant, heterogeneous bile duct malignancy with poor treatment options. A novel type of cell death termed cuproptosis was recently demonstrated to closely correlate with tumor progression. To gain more insight into the role of cuproptosis in CCA, we investigated the prognostic implications of cuproptosis related genes (CRGs) and their relationship to the development of CCA.MethodsGene expression data for CCA were obtained from the European Bioinformatics Institute (EMBL-EBI) database. Least absolute shrinkage and selection operator (LASSO) penalized Cox regression was used to construct a prognostic risk model based on CRGs. RNA-seq, qRT−PCR and immunohistochemistry staining were used to verify the expression of CRGs in human CCA tissues or cell lines. Further in vitro experiments were performed to demonstrate the role of cuproptosis in CCA.ResultsWe established a 4-gene signature (ATP7A, FDX1, DBT and LIAS) that exhibited good stability and was an independent prognostic factor for CCA. Seventy-five CCA samples were divided into high- and low-risk groups based on the risk score. Enrichment analysis revealed increased extracellular activity in the high-risk group and increased lipid metabolic activity in the low-risk group. Moreover, the 4 signature genes were verified in clinical samples and cell lines by RNA-seq, qRT−PCR and immunohistochemistry. Further experiments confirmed that cuproptosis can significantly inhibit the viability of CCA cells. Knockdown of the key gene LIAS ameliorated the toxicity of cuproptosis to CCA cells.ConclusionWe established a 4-gene prognostic signature based on cuproptosis and explored the role of cuproptosis in CCA. The results provide an effective indicator for predicting the prognosis of cuproptosis in CCA.

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“…Furthermore, it is suggested that targeting of IGF2BP1 may provide a treatment option for OC. Studies focused on the binding of IGF2BP2 to circRNA indicate that the IGF2BP2-circRNA complex promotes cisplatin resistance or progression in OC (Fu et al, 2022;Ji et al, 2022;H. Li, Luo, et al, 2022;.…”

Section: A Readersmentioning

confidence: 99%

“…Furthermore, it is suggested that targeting of IGF2BP1 may provide a treatment option for OC. Studies focused on the binding of IGF2BP2 to circRNA indicate that the IGF2BP2‐circRNA complex promotes cisplatin resistance or progression in OC (Fu et al, 2022; Ji et al, 2022; H. Li, Luo, et al, 2022; S. Wang, Li, et al, 2021). For example, circITGB6 specifically binds to the KH1‐2 structural domain of IGF2BP2, enhancing mRNA stability of FGF9 (H. Li, Luo, et al, 2022).…”

Section: Rna Modifications In Ocmentioning

confidence: 99%

“…This further promotes the polarization of tumor‐associated macrophage (TAM) to the M2 phenotype, inducing cisplatin resistance in OC (H. Li, Luo, et al, 2022). IGF2BP2 can also bind to circPBX3 and enhance the stability of ATP7A mRNA, thereby promoting cisplatin resistance in OC cells (Fu et al, 2022). These findings provide a mechanistic framework to address cisplatin resistance during OC treatment.…”

Section: Rna Modifications In Ocmentioning

confidence: 99%

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RNA epigenetic modifications in ovarian cancer: The changes, chances, and challenges

Yao

et al. 2023

WIREs RNA

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Ovarian cancer (OC) is the most common female cancer worldwide. Patients with OC have high mortality because of its complex and poorly understood pathogenesis. RNA epigenetic modifications, such as m6A, m1A, and m5C, are closely associated with the occurrence and development of OC. RNA modifications can affect the stability of mRNA transcripts, nuclear export of RNAs, translation efficiency, and decoding accuracy. However, there are few overviews that summarize the link between m6A RNA modification and OC. Here, we discuss the molecular and cellular functions of different RNA modifications and how their regulation contributes to the pathogenesis of OC. By improving our understanding of the role of RNA modifications in the etiology of OC, we provide new perspectives for their use in OC diagnosis and treatment.This article is categorized under: RNA Processing > RNA Editing and Modification RNA in Disease and Development > RNA in Disease

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Circular RNA circPBX3 promotes cisplatin resistance of ovarian cancer cells via interacting with IGF2BP2 to stabilize ATP7A mRNA expression

Cited by 15 publications

References 38 publications

Insulin-like growth factor 2 mRNA-binding protein 2 is a therapeutic target in ovarian cancer

Insulin-like growth factor 2 mRNA-binding protein 2 is a therapeutic target in ovarian cancer

Establishment and experimental validation of a novel cuproptosis-related gene signature for prognostic implication in cholangiocarcinoma

RNA epigenetic modifications in ovarian cancer: The changes, chances, and challenges

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