Effect and mechanism of <scp>circRNAs</scp> in tumor angiogenesis and clinical application

Zhao, Lei; Guo, Yuying; Guo, Yaxin; Ji, Xiang; Fan, Dandan; Chen, Chen; Yuan, Weitang; Sun, Zhenqiang; Ji, Zhenyu

doi:10.1002/ijc.33863

Cited by 19 publications

(12 citation statements)

References 74 publications

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“…First, our study did not include enough clinical samples, and there was a lack of relevant follow-up prognostic information, which made it difficult for us to analyze the correlation between circPOLR2A expression and cRCC prognosis. Due to the stability of circRNAs endowed by their loop structure, several studies have demonstrated the clinical application potential of circRNAs as cancer biomarkers [77,[82][83][84]. Hence, including more cRCC samples with sufficient follow-up data is necessary for evaluating the clinical value of circPOLR2A in future research, which is of great significance for subsequent clinical transformation.…”

Section: Discussionmentioning

confidence: 99%

Circular RNA circPOLR2A promotes clear cell renal cell carcinoma progression by facilitating the UBE3C-induced ubiquitination of PEBP1 and, thereby, activating the ERK signaling pathway

Chen

Liu

et al. 2022

Mol Cancer

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Background Increasing evidence has demonstrated that circular RNAs (circRNAs) are implicated in cancer progression. However, the aberrant expression and biological functions of circRNAs in clear cell renal cell carcinoma (cRCC) remain largely elusive. Method Differentially expressed circRNAs in cRCC were filtered via bioinformatics analysis. Aberrant circPOLR2A expression was validated in cRCC tissues and cell lines via qRT-PCR. Sanger sequencing was used to identify the backsplicing site of circPOLR2A. In vitro and in vivo functional experiments were performed to evaluate the role of circPOLR2A in cRCC malignancy. RNA pull-down, mass spectrometry, RIP, FISH and immunofluorescence assays were used to identify and validate the circPOLR2A-interacting proteins. Ubiquitination modification and interaction between proteins were detected via Co-IP and western blotting. The m6A modification in circPOLR2A was validated by the meRIP assay. Results Bioinformatics analysis revealed that circPOLR2A was highly expressed in cRCC tissues and metastatic cRCC tissues. CircPOLR2A expression was associated with tumor size and TNM stage in cRCC patients. In vitro and in vivo functional assays revealed that circPOLR2A accelerated cRCC cell proliferation, migration, invasion and angiogenesis, while inhibiting apoptosis. Further mechanistic research suggested that circPOLR2A could interact with UBE3C and PEBP1 proteins, and that UBE3C could act as a specific ubiquitin E3 ligase for the PEBP1 protein. The UBE3C/circPOLR2A/PEBP1 protein-RNA ternary complex enhanced the UBE3C-mediated ubiquitination and degradation of the PEBP1 protein which could inactivate the ERK signaling pathway. Rescue experiments revealed that the PEBP1 protein was the functional downstream target of circPOLR2A. Furthermore, m6A modification in circPOLR2A was confirmed, and the m6A reader YTHDF2 could regulate circPOLR2A expression. Conclusion Our study demonstrated that circPOLR2A modulated the UBE3C-mediated ubiquitination and degradation of the PEBP1 protein, and further activated the ERK pathway during cRCC progression and metastasis. The m6A reader, YTHDF2, regulated circPOLR2A expression in cRCC. Hence, circPOLR2A could be a potential target for the diagnosis and treatment of cRCC.

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Section: Discussionmentioning

confidence: 99%

Circular RNA circPOLR2A promotes clear cell renal cell carcinoma progression by facilitating the UBE3C-induced ubiquitination of PEBP1 and, thereby, activating the ERK signaling pathway

Chen

Liu

et al. 2022

Mol Cancer

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“… 17 CircRNAs are characterized as being stable, specific, and well conserved and have been suggested to be vital participants in carcinogenesis, making them possible candidates for cancer screening. 18 , 19 , 20 Accordingly, circRNAs have attracted more attention in tumor pathogenesis and biomarker research in recent years. In the field of GC, a number of abnormally expressed circRNAs have been discovered, and their functions and molecular mechanisms have been revealed.…”

Section: Discussionmentioning

confidence: 99%

“…The rapid development of biological technologies has contributed to the in‐depth exploration of functional circRNAs 17 . CircRNAs are characterized as being stable, specific, and well conserved and have been suggested to be vital participants in carcinogenesis, making them possible candidates for cancer screening 18‐20 . Accordingly, circRNAs have attracted more attention in tumor pathogenesis and biomarker research in recent years.…”

Section: Discussionmentioning

confidence: 99%

Biological and clinical implications of hsa_circ_0086720 in gastric cancer and its clinical application

Shao

Yan

et al. 2022

Clinical Laboratory Analysis

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Background Circular RNAs (circRNAs) are thought to be vital participants in carcinogenesis and have the characteristics of being stable, specific, and well conserved. However, their clinical significance and application value in gastric cancer (GC) are still poorly understood. Hsa_circ_0086720 was found to be a dysregulated circRNA in GC by microarray screening and was further explored for its clinical significance and application. Methods Hsa_circ_0086720 was detected in GC cell lines, tissues, and plasma, and the clinicopathological correlations were investigated. The existence, stability, origin, and change in the plasma hsa_circ_0086720 level were verified in early GC patients. Moreover, receiver operating characteristic and Kaplan–Meier survival curves were constructed to analyze the diagnostic and prognostic values, and bioinformatics analysis was used to identify the potential functions. Finally, risk factors and nomogram predicting were established. Results Hsa_circ_0086720 was found to be downregulated in gastric carcinogenesis, and tissue hsa_circ_0086720 was negatively associated with perineural invasion, Borrmann type, disease‐free survival, and overall survival. Hsa_circ_0086720 was stable in circulating plasma and was actively secreted by cells in gastric carcinogenesis. As a biomarker for early GC screening, plasma hsa_circ_0086720 had good sensitivity and specificity, and its stability met the clinical application requirements. Bioinformatics analysis suggested that dysregulated hsa_circ_0086720 has important functions in gastric carcinogenesis. Univariate Cox regression analysis identified factors associated with overall survival time and disease‐free survival time. The nomograms showed good accuracy of predicting survival time. Conclusion Hsa_circ_0086720 is a novel biomarker for screening early GC and predicting the prognosis of advanced‐stage patients.

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“…A growing body of literature has long shown that mRNAs, miRNAs, lncRNAs, and circRNAs can be used as diagnostic and prognostic biomarkers for certain cancers [23,24,25,26,27,28]. Genetic signature-based risk models have also been widely reported to show high prognostic accuracy in many other cancer types [29,30,31,32].…”

Section: Discussionmentioning

confidence: 99%

Identification of a cuproptosis related chromatin regulators signature for lung adenocarcinoma

Wei

Yang

et al. 2022

Preprint

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Background: Lung adenocarcinoma (LUAD) is the leading cause of cancer-related mortality worldwide, displaying dismal prognosis. Growing evidence now links cuproptosis related genes (CRGs) and chromatin regulators (CRs) to cancer progression. However, the relationship between CRGs and CRs is not yet fully understood. Therefore, we aimed to reveal the connection and prognostic value of these two factors in LUAD patients. Methods: Cuproptosis related genes (CRGs) and chromatin regulators (CRs) were retrieved from previous top studies. For TCGA analysis, mRNA expression andclinical information for LUAD were downloaded via R package. Functional enrichment was analyzed through the ClusterProfler package. Cox regression analysis and LASSO regression analysis were utilized to train models for predicting outcome in LUAD. The Kaplan-Meier curve analyses was used to assess the prognosis for cases categorized as High-risk and Low-risk groups. DsigDB dataset was performed to screen the potential drugs for LUAD treatment. Results: We visualized an protein-protein interaction (PPI) network between CRGs and CRs. Functional analysis suggested that CRs were mainly enriched in chromatin modification and cell cycle pathways. The prognosis prediction model was successfully constructed and validated for the patients with LUAD. Moreover, we also showed 11-CRs-based model was an independent prognostic factor for LUAD patients. This CR-based model was associated with immune cells infiltration as well as immune checkpoint. Seven prospective drugs was detected for the treatment of LUAD patients. Conclusion: In conclusion, our findings provide unique information not available in previous studies, casting novel insights about the correlation between CRGs and CRs in LUAD. We also identified several prognostic biomarkers for the survival of patients with LUAD.

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Effect and mechanism of circRNAs in tumor angiogenesis and clinical application

Cited by 19 publications

References 74 publications

Circular RNA circPOLR2A promotes clear cell renal cell carcinoma progression by facilitating the UBE3C-induced ubiquitination of PEBP1 and, thereby, activating the ERK signaling pathway

Circular RNA circPOLR2A promotes clear cell renal cell carcinoma progression by facilitating the UBE3C-induced ubiquitination of PEBP1 and, thereby, activating the ERK signaling pathway

Biological and clinical implications of hsa_circ_0086720 in gastric cancer and its clinical application

Identification of a cuproptosis related chromatin regulators signature for lung adenocarcinoma

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