Circ-ZNF609 regulates G1-S progression in Rhabdomyosarcoma
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA482643 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7588310_1.fastq.gz | Fastqsanger.gz | |||
| SRR7588310_2.fastq.gz | Fastqsanger.gz | |||
| SRR7588311_1.fastq.gz | Fastqsanger.gz | |||
| SRR7588311_2.fastq.gz | Fastqsanger.gz | |||
| SRR7588312_1.fastq.gz | Fastqsanger.gz |
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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:Circular RNAs (circRNAs) represent a class of covalently closed RNAs, derived from non-canonical splicing events, which are expressed in all eukaryotes and often conserved among different species. We previously showed that the circRNA originating from the ZNF609 locus (circ-ZNF609) acts as a crucial regulator of human primary myoblast growth: indeed, the downregulation of the circRNA, and not of its linear counterpart, strongly reduced the proliferation rate of in vitro cultured myoblasts. 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 upregulated in biopsies from the two major RMS subtypes, embryonal (ERMS) and alveolar (ARMS). Moreover, we discovered that in an ERMS-derived cell line circ-ZNF609 knock-down induced a specific block at the G1-S transition, a strong decrease of p-Akt protein level and an alteration of the pRb/Rb ratio. Regarding p-Akt, we were able to show that circ-ZNF609 acts by counteracting p-Akt proteasome-dependent degradation, thus working as a new regulator of cell proliferation-related pathways. As opposed to ERMS-derived cells, the circRNA depletion had no cell cycle effects in ARMS-derived cells. Since in these cells the p53 gene resulted downregulated, with a concomitant upregulation of its cell cycle-related target genes, we suggest that this could account for the lack of circ-ZNF609 effect in ARMS.
| S-EPMC6544520 | biostudies-literature
Project description:Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the digestive tract. The majority of GIST patients eventually develop resistance to imatinib therapy. To identify the responsible mechanisms, we investigated the differentially expressed mRNAs and circRNAs in imatinib-resistant GISTs using SBC ceRNA microarrays. We found that 107 mRNAs and 521 circRNAs were significantly differentially expressed between imatinib-naïve and imatinib-resistant GIST tissue samples. qRT-PCR analyses validated that circ-BRIP1, circ-EPHB4 and circ-RECQL4 and their host genes were upregulated in imatinib-resistant GISTs, and circ-BRIP1, circ-EPHB4, and RECQL4 were associated with imatinib resistance, tumor relapse and progression, and metastasis in GIST patients. The expression levels of circ-BRIP1, circ-EPHB4 and their host genes were also evaluated using TMAs with 150 human GISTs. The expression level of EPHB4 was significantly increased in high-grade GISTs in comparison to low-grade GISTs and correlated with imatinib resistance. Specifically, we first developed a method for high-throughput analysis of the expression of differentially expressed circRNAs by ISH-IHC in a set of FFPE-tissue microarrays in GIST. Our results also suggested a possible role for circ-BRIP1, circ-EPHB4, and their host genes in the progression of GISTs.
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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: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.
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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.
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