Splicing factor derived circular RNA circCAMSAP1 accelerates nasopharyngeal carcinoma tumorigenesis via a SERPINH1/c-Myc positive feedback loop

Wang, Yian; Yan, Qijia; Mo, Yongzhen; Liu, Yuhang; Wang, Yumin; Zhang, Shanshan; Guo, Can; Wang, Fuyan; Li, Guiyuan; Zeng, Zhaoyang; Xiong, Wei

doi:10.1186/s12943-022-01502-2

Cited by 44 publications

(26 citation statements)

References 98 publications

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“…Interestingly, circPVT1 competitively occupied the c-Myc-binding domain on β-TrCP to prevent β-TrCPinduced c-Myc ubiquitination and degradation, thus enhancing NPC cell migration and invasion. CircRNAs function as signaling pathway regulators in gene expression and other important cellular processes [31][32][33][34][35][36]. For example, circRNAs may act as scaffolds or decoys of RNAbinding proteins (RBPs) to form nuclear or cytoplasmic complexes [39][40][41].…”

Section: Discussionmentioning

confidence: 99%

Circular RNA circPVT1 promotes nasopharyngeal carcinoma metastasis via the β-TrCP/c-Myc/SRSF1 positive feedback loop

Wang

et al. 2022

Mol Cancer

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Background Circular RNAs (circRNAs) act as gene expression regulators and are involved in cancer progression. However, their functions have not been sufficiently investigated in nasopharyngeal carcinoma (NPC). Methods The expression profiles of circRNAs in NPC cells within different metastatic potential were reanalyzed. Quantitative reverse transcription PCR and in situ hybridization were used to detect the expression level of circPVT1 in NPC cells and tissue samples. The association of expression level of circPVT1 with clinical properties of NPC patients was evaluated. Then, the effects of circPVT1 expression on NPC metastasis were investigated by in vitro and in vivo functional experiments. RNA immunoprecipitation, pull-down assay and western blotting were performed to confirm the interaction between circPVT1 and β-TrCP in NPC cells. Co-immunoprecipitation and western blotting were performed to confirm the interaction between β-TrCP and c-Myc in NPC cells. Results We find that circPVT1, a circular RNA, is significantly upregulated in NPC cells and tissue specimens. In vitro and in vivo experiments showed that circPVT1 promotes the invasion and metastasis of NPC cells. Mechanistically, circPVT1 inhibits proteasomal degradation of c-Myc by binding to β-TrCP, an E3 ubiquiting ligase. Stablization of c-Myc by circPVT1 alters the cytoskeleton remodeling and cell adhesion in NPC, which ultimately promotes the invasion and metastasis of NPC cells. Furthermore, c-Myc transcriptionally upregulates the expression of SRSF1, an RNA splicing factor, and recruits SRSF1 to enhance the biosynthesis of circPVT1 through coupling transcription with splicing, which forms a positive feedback for circPVT1 production. Conclusions Our results revealed the important role of circPVT1 in the progression of NPC through the β-TrCP/c-Myc/SRSF1 positive feedback loop, and circPVT1 may serve as a prognostic biomarker or therapeutic target in patients with NPC.

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Section: Discussionmentioning

confidence: 99%

Circular RNA circPVT1 promotes nasopharyngeal carcinoma metastasis via the β-TrCP/c-Myc/SRSF1 positive feedback loop

Wang

et al. 2022

Mol Cancer

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“…Due to advances made in next-generation sequencing technologies in recent years, a growing number of circRNAs have been discovered to be involved in the control of a range of human disease processes. Although recent studies have shown numerous circRNAs play an indispensable role in the occurrence and progress of NPC (19)(20)(21)(22)(23), their function in its onset and progress or specific mechanisms of circRNA in the disease are still insufficient.…”

Section: Discussionmentioning

confidence: 99%

CircHIPK2 promotes proliferation of nasopharyngeal carcinoma by down-regulating HIPK2

Zhang¹,

Huang²,

Sun³

et al. 2022

Transl Cancer Res TCR

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Background: Circular RNAs (circRNAs) are a new family of endogenous non-coding RNAs generated by a covalently closed loop, and a mounting body of data suggests they control gene expression. While the circRNA-homeodomain-interacting protein kinase-2 (circHIPK2) is generated from the homeodomaininteracting protein kinase 2 (HIPK2) gene, the function of circHIPK2 in nasopharyngeal cancer (NPC) along with the responsible mechanisms are still unclear.Methods: RNA-sequencing data was utilized to determine the differentially expressed circRNAs, and circHIPK2 was established as a novel prospective circRNA. The expressions of circRNAs along with messenger RNAs (mRNAs) in NPC tissues and cells was assessed via quantitative real-time polymerase chain reaction (qRT-PCR), and the transfection of NPC cells with plasmids in vitro and in vivo was adopted to explore the effects of circHIPK2 in NPC. Western blotting was adopted to assess the expressions of HIPK2 and β-catenin, while Cell Counting Kit (CCK)-8 assay coupled with colony-forming assay were utilized to assess the biological functions. The expression of nuclear and cytoplasmic HIPK2 was detected via nucleocytoplasmic separation assay.Results: Herein, we established that circHIPK2 was upregulated in NPC tissues. Over-expression of circHIPK2 promoted cell proliferation in vitro and in vivo, and further studies revealed it inhibited the protein level of HIPK2 in a post-transcriptional pattern, decreasing β-catenin expression and suppressing the proliferation of NPC.Conclusions: Our findings demonstrated elevated circHIPK2 facilitated the cell proliferation of NPC cells via the circHIPK2/HIPK2 axis, suggesting circHIPK2 might be an oncogene to promote the process of NPC and could be a novel treatment target for its management.

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“…Discussion BRD7 was con rmed as a critical member of the bromodomain protein family and transcription factor family and functions as a tumor suppressor in several tumors, such as NPC [6,7,8,9,10,28,29,30]. Increasing evidences have indicated that many protein coding genes contain circular RNA forms, which play critical biological roles as oncogenes or tumor suppressors in the occurrence and development of NPC [13,14,15,16,17,31]. For example, circRNF13, a circular RNA encoded by the RNF13 gene, acts as a tumor suppressor gene to inhibit the glycolysis-regulated AMPK-mTOR pathway through the circrNF13-SUMO2-GLUT1 axis, thereby inhibiting the proliferation and metastasis of NPC [13].…”

Section: Expression and Clinical Correlation Of Circbrd7 And Brd7 In ...mentioning

confidence: 99%

CircBRD7 inhibits tumor growth and metastasis in nasopharyngeal carcinoma via forming a positive feedback regulation loop with its host gene

Wei

Chen

et al. 2022

Preprint

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Background: BRD7 was identified as a tumor suppressor in nasopharyngeal carcinoma (NPC). Circular RNA (CircRNAs) are involved in the occurrence and development of NPC as oncogenes or tumor suppressors. However, the function and mechanism of the circRNAs derived from BRD7 in NPC are not well understood. Methods: Bioinformatics analysis, agarose gel electrophoresis and Sanger sequencing were performed to screen and identify the circular RNA derived from BRD7. CCK-8, colony formation, wound healing and transwell assays were used to evaluate the cell proliferation, migration and invasion abilities of circBRD7. The ChIP-qPCR assay was performed to investigate the regulatory mechanism of circBRD7 on BRD7. Xenograft tumor and lung metastasis models were constructed to confirm the effect of circBRD7 on tumor growth and metastasis. Results: CircBRD7 was identified as a circular RNA derived from BRD7 that inhibited cell proliferation, migration, invasion of NPC cells as well as the xenograft tumor growth and metastasis in vivo. Mechanistically,circBRD7 promoted the transcription and expression of BRD7 by enhancing the enrichment of H3K27ac in the promoter region of its host gene, and BRD7 promoted the expression of circBRD7, thus circBRD7 formed positive feedback loop with BRD7 to inhibit NPC development and progression. Moreover, restoration of BRD7 expression rescued the inhibitory effect of circBRD7 on the proliferation, migration and invasion of NPC cell and xenograft tumor growth and metastasis. In addition, circBRD7 was expressed at low levels in NPC tissues, which was positively correlated with BRD7 expression and negatively correlated with the clinical stage of NPC patients. The combination of circBRD7 and BRD7 could be used as an important molecular marker for the evaluation of NPC progression. Conclusions: Taken together, circBRD7 inhibits the tumor growth and metastasis of NPC via forming positive feedback loop with its host gene, and targeting the circBRD7/BRD7 axis is a promising strategy for the clinical diagnosis and treatment of NPC.

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Splicing factor derived circular RNA circCAMSAP1 accelerates nasopharyngeal carcinoma tumorigenesis via a SERPINH1/c-Myc positive feedback loop

Cited by 44 publications

References 98 publications

Circular RNA circPVT1 promotes nasopharyngeal carcinoma metastasis via the β-TrCP/c-Myc/SRSF1 positive feedback loop

Circular RNA circPVT1 promotes nasopharyngeal carcinoma metastasis via the β-TrCP/c-Myc/SRSF1 positive feedback loop

CircHIPK2 promotes proliferation of nasopharyngeal carcinoma by down-regulating HIPK2

CircBRD7 inhibits tumor growth and metastasis in nasopharyngeal carcinoma via forming a positive feedback regulation loop with its host gene

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