Circ-ZNF609 regulates G1-S progression in Rhabdomyosarcoma
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ABSTRACT:
PROVIDER: PRJNA482643 | ENA |
REPOSITORIES: ENA
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Project description:Circular RNAs (circRNAs) represent a class of covalently closed RNAs, derived from a non-canonical splicing event, ubiquitously expressed among Eukaryotes and conserved among different species. We identified a circRNA (circ-ZNF609) involved in the regulation of human primary myoblast proliferation. Upon its depletion, the percentage of proliferating myoblasts was highly reduced. To deepen our knowledge about circ-ZNF609 role in cell cycle regulation, we studied its expression and function in Rhabdomyosarcoma (RMS), a pediatric skeletal muscle malignancy. We found that circ-ZNF609 is up-regulated in biopsies from both the two major RMS subtypes, the alveolar (ARMS) and the embryonal (ERMS), and we discovered that its knock-down blocks proliferation of an ERMS-derived cell line, while it has no effect on ARMS-derived cells. To understand the mechanism through which circ-ZNF609 affects cell proliferation we compared the different effects of circ-ZNF609 depletion in ERMS and ARMS and we identified genes and pathways on which the circRNA acts.
2018-12-14 | GSE117609 | GEO
Project description: Not available
| S-EPMC6544520 | biostudies-literature
Project description:Objective: Esophageal squamous carcinoma (ESCC) is one of the most common gastrointestinal tumors, and the PI3K/AKT signaling pathway plays a key role in the development of ESCC. circRNAs have been reported to be involved in the regulation of PI3K/AKT signaling, but the underlying mechanisms are unclear. This study aimed to identify protein-coding circRNAs and investigate their function in ESCC. Design: Differential expression of circRNAs between ESCC tissues and adjacent normal tissues was identified using circRNA microarray analysis. A novel protein encoded by circ-PDE5A was identified by LC-MS/MS. Molecular biological methods were used to explore the biological functions and regulatory mechanisms of circ-PDE5A and its encoded PDE5A-500aa novel protein in ESCC. Construction of a nanoplatform for the coupling of circRNAs to investigate the therapeutic translation value of circ-PDE5A. Results: We found that circ-PDE5A expression was downregulated in ESCC cells and tissues, and its low expression was associated with later clinicopathological staging and poorer prognosis. Functionally, circ-PDE5A inhibited ESCC proliferation and metastasis in vitro and in vivo by encoding the novel PDE5A-500aa protein, which was identified as a key player in regulating PI3K/AKT signaling activation in ESCC. Mechanistically, the novel PDE5A-500aa protein binds directly to PIK3IP1 and promotes USP14-mediated deubiquitination of the k48-linked polyubiquitin chain at residue K198 of PIK3IP1, thereby attenuating PI3K/AKT pathway in ESCC. In addition, the circ-PDE5A plasmid-coupled reduction-responsive nanoplatform successfully inhibited ESCC growth and metastasis. Conclusions: circ-PDE5A represents an epigenetic mechanism regulating PI3K/ATK signaling and serves as a novel and promising therapeutic target and prognostic marker for ESCC.
2024-01-15 | GSE250413 | GEO
Project description:Circular RNAs (circRNAs), a class of covalently closed RNA formed by a back-splicing reaction, have been involved in the regulation of diverse oncogenic processes. In this article we describe circVAMP3, a novel circular RNA overexpressed in alveolar rhabdomyosarcoma. We demonstrate that circVAMP3 has a differential m6A pattern opposed to its linear counterpart, suggesting that the two isoforms can be differently regulated by such RNA modification although their sequence similarity. Moreover, we show how circVAMP3 depletion in alveolar rhabdomyosarcoma cells can impair cell cycle progression, e.g. through the downregulation of the AKT pathway, pointing to this non-coding RNA as a novel regulator of the alveolar rhabdomyosarcoma progression and a putative future therapeutic target.
2021-08-03 | GSE174397 | GEO
Project description:Rhabdomyosarcoma is a soft tissue cancer that arises in skeletal muscle due to mutations in myogenic progenitors that lead to ineffective differentiation and malignant transformation. The transcription factors Pax3 and Pax7 and their down-stream target genes are tightly linked with the fusion positive alveolar subtype, whereas the RAS pathway is usually involved in the embryonic, non-fusion variant. Here, we analyse the role of Pax3 in a non-fusion context, by linking alterations in gene expression in pax3a/pax3b double mutant zebrafish with tumour progression in kRAS-induced rhabdomyosarcoma tumours. Several genes in the RAS signalling pathway, including MAPK signalling pathway, were significantly down-regulated in pax3a/pax3b double mutant zebrafish. Onset and progression of rhabdomyosarcoma tumours were also delayed in the pax3a/pax3b double mutant zebrafish indicating that Pax3 transcription factors have an unappreciated role in mediating malignancy also in non-fusion rhabdomyosarcoma.
2022-10-19 | GSE208266 | GEO
Project description:Circular RNAs (circRNAs), a subclass of noncoding RNAs characterized by covalently closed continuous loops, play emerging roles in tumorigenesis and aggressiveness. However, the functions and underlying mechanisms of circRNAs in regulating neuroblastoma progression still remain elusive. We identify one circRNA derived from CUX1 (circ-CUX1) as a novel driver of neuroblastoma progression. To investigate the mechanisms underlying the oncogenic functions of circ-CUX1, we employed the Illumina HiSeq X Ten as a discovery platform to analyze the transcriptome profiling changes of human neuroblastoma IMR32 cells in response to stable over-expression of circ-CUX1. The results showed that stable over-expression of circ-CUX1 led to altered expression of 1215 human mRNAs, including 781 up-regulated genes and 434 down-regulated genes. Furthermore, we validated the RNA-seq results by real-time RT-PCR with high identity. Overall, our results provided fundamental information about the transcriptomic changes in response to circ-CUX1 over-expression in human tumor cells, and these findings will help us understand the pathogenesis of tumor progression.
2019-11-07 | GSE136135 | GEO
Project description:In this study we characterized the importance of CDK12-kinase activity in cell cycle regulation, using CDK12 anolog-sentive cells. Inhibition of analog-sensitive CDK12 reveals its catalytic activity is necessary for optimal G1/S progression. Mechanistically, CDK12 regulates transcription of core DNA replication genes and affects timely assembly of pre-replication DNA complex on chromatin. We have performed 3’-end RNA-sequencing after CDK12 inhibition and identified that the expression of core DNA replication genes were affected. To investigate further, we carried out nuclear RNA-seq coupled with ChIP-seq, and demonstrated that CDK12 regulates RNAPII processivity of core DNA replication genes and optimal G1/S progression.
2019-07-22 | GSE120069 | GEO
Project description:In this study we characterized the importance of CDK12-kinase activity in cell cycle regulation, using CDK12 anolog-sentive cells. Inhibition of analog-sensitive CDK12 reveals its catalytic activity is necessary for optimal G1/S progression. Mechanistically, CDK12 regulates transcription of core DNA replication genes and affects timely assembly of pre-replication DNA complex on chromatin. We have performed 3’-end RNA-sequencing after CDK12 inhibition and identified that the expression of core DNA replication genes were affected. To investigate further, we carried out nuclear RNA-seq coupled with ChIP-seq, and demonstrated that CDK12 regulates RNAPII processivity of core DNA replication genes and optimal G1/S progression.
2019-07-22 | GSE120071 | GEO
Project description:In this study we characterized the importance of CDK12-kinase activity in cell cycle regulation, using CDK12 anolog-sentive cells. Inhibition of analog-sensitive CDK12 reveals its catalytic activity is necessary for optimal G1/S progression. Mechanistically, CDK12 regulates transcription of core DNA replication genes and affects timely assembly of pre-replication DNA complex on chromatin. We have performed 3’-end RNA-sequencing after CDK12 inhibition and identified that the expression of core DNA replication genes were affected. To investigate further, we carried out nuclear RNA-seq coupled with ChIP-seq, and demonstrated that CDK12 regulates RNAPII processivity of core DNA replication genes and optimal G1/S progression.
2019-07-22 | GSE120070 | GEO
Project description:Circular RNAs (circRNAs), a subclass of noncoding RNAs characterized by covalently closed continuous loops, play emerging roles in tumorigenesis and aggressiveness. However, the functions and underlying mechanisms of circRNAs in regulating the Wnt/β-catenin signaling and cancer progression still remain elusive. We identify one intronic circRNA derived from CTNNB1 (circ-CTNNB1) as a novel driver of cancer progression. To investigate the mechanisms underlying the oncogenic functions of circ-CTNNB1, we employed the Illumina HiSeq X Ten as a discovery platform to analyze the transcriptome profiling changes of human gastric cancer AGS cells in response to stable over-expression of circ-CTNNB1. The results showed that stable over-expression of circ-CTNNB1 led to altered expression of 2230 human mRNAs, including 1244 up-regulated genes and 986 down-regulated genes. Furthermore, we validated the RNA-seq results by real-time RT-PCR with high identity. Overall, our results provided fundamental information about the transcriptomic changes in response to circ-CTNNB1 over-expression in human cancer cells, and these findings will help us understand the pathogenesis of cancer progression.
2019-09-30 | GSE120496 | GEO