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Dysregulation of p53-RBM25-mediated circAMOTL1L biogenesis contributes to prostate cancer progression (Agilent circRNA data set)

ABSTRACT: To explore the molecular mechanisms underlying circRNA role in prostate carcinogenesis and progression of PCa, we first used circular RNA microarrays to acquire circRNA profiles in PCa tissues. Five pairs of samples were taken from the two different areas, i.e., high-grade PCa (Gleason>8) and low-grade PCa (Gleason< 6), within the same PCa sample

ORGANISM(S): Homo sapiens

PROVIDER: GSE113153 | GEO | 2020/08/27

REPOSITORIES: GEO

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Dysregulation of p53-RBM25-mediated circAMOTL1L biogenesis contributes to prostate cancer progression (Agilent circRNA data set)

Project description:Dysregulation of p53-RBM25-mediated circAMOTL1L biogenesis contributes to prostate cancer progression (Agilent circRNA data set)

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Dysregulation of p53-RBM25-mediated circAMOTL1L biogenesis contributes to prostate cancer progression (RNA-seq data set)

Project description:To clarify the effect of p53 on RBP gene expression, we knocked out p53 gene in PC3 cells to generate p53 knockout stable cell line (p53-/- PC3 cells) and examined the expression of the known RBP genes by RNA sequencing.

2020-08-27 | GSE113179 | GEO

Human circRNA expression profiling in plasma sample of hepatocellular carcinoma

Project description:Arraystar Human circRNA Microarray is designed for the global profiling of human circRNAs. In this study, we applied a circRNA microarray to screen the potential biomarker for HCC. 20 samples extracted from plasma samples including HCC group before operation, and after operation, CH group and control group. Each group contained five samples.

2021-03-02 | E-MTAB-8799 | biostudies-arrayexpress

Conserved regulation of ZC3H14/Nab2 in circRNA biogenesis

Project description:Circular RNAs (circRNAs) are natural outputs of eukaryotic transcription and RNA processing and have emerged as critical regulators in physiology and human diseases. Although a series of cis-elements and trans-factors are reported to globally regulate circRNA biogenesis, most of these regulations are unconserved or at most mammalian conserved. Here, using a genome-wide CRISPR knockout screen, we have identified an evolutionarily conserved polyadenosine RNA-binding protein ZC3H14 to regulate circRNA biogenesis in eukaryotes. Mechanistically, ZC3H14 associates with spliceosome to bind to 3' and 5' exon-intron boundaries of circularized exons, and forms a dimer to promote circRNA biogenesis. ZC3H14 knockout mice exhibit disrupted spermatogenesis and reduced testicular circRNA levels. Additionally, human ZC3H14 is associated with male infertility. Our findings reveal a conserved requirement for ZC3H14/Nab2 in the modulation of eukaryotic backsplicing and link ZC3H14 along with circRNAs to mammalian testicular disorders.

2024-02-10 | GSE254916 | GEO

Regulation of circRNA biogenesis.

Project description:Unlike linear RNAs terminated with 5' caps and 3' tails, circular RNAs are characterized by covalently closed loop structures with neither 5' to 3' polarity nor polyadenylated tail. This intrinsic characteristic has led to the general under-estimation of the existence of circular RNAs in previous polyadenylated transcriptome analyses. With the advent of specific biochemical and computational approaches, a large number of circular RNAs from back-spliced exons (circRNAs) have been identified in various cell lines and across different species. Recent studies have uncovered that back-splicing requires canonical spliceosomal machinery and can be facilitated by both complementary sequences and specific protein factors. In this review, we highlight our current understanding of the regulation of circRNA biogenesis, including both the competition between splicing and back-splicing and the previously under-appreciated alternative circularization.

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Identification of circRNA-interacting proteins in pancreatic ductal adenocarcinoma

Project description:Many studies have demonstrated the importance of circRNA in regulating gene expression through functioning as microRNA sponges. However, the roles of circRNA-protein interaction are not fully understood. Importantly, how circRNA-protein interaction contributes the progression of pancreatic ductal adenocarcinoma is largely unexplored. Therefore, RNA Pull down assay for investigating RNA-protein interaction was performed in PANC-1 cells.

2022-02-15 | PXD015048 | Pride

Dysregulation of p53-RBM25-mediated circAMOTL1L biogenesis contributes to prostate cancer progression through the circAMOTL1L-miR-193a-5p-Pcdha pathway.

Project description:p53, circRNAs and miRNAs are important components of the regulatory network that activates the EMT program in cancer metastasis. In prostate cancer (PCa), however, it has not been investigated whether and how p53 regulates EMT by circRNAs and miRNAs. Here we show that a Amotl1-derived circRNA, termed circAMOTL1L, is downregulated in human PCa, and that decreased circAMOTL1L facilitates PCa cell migration and invasion through downregulating E-cadherin and upregulating vimentin, thus leading to EMT and PCa progression. Mechanistically, we demonstrate that circAMOTL1L serves as a sponge for binding miR-193a-5p in PCa cells, relieving miR-193a-5p repression of Pcdha gene cluster (a subset of the cadherin superfamily members). Accordingly, dysregulation of the circAMOTL1L-miR-193a-5p-Pcdha8 regulatory pathway mediated by circAMOTL1L downregulation contributes to PCa growth in vivo. Further, we show that RBM25 binds directly to circAMOTL1L and induces its biogenesis, whereas p53 regulates EMT via direct activation of RBM25 gene. These findings have linked p53/RBM25-mediated circAMOTL1L-miR-193a-5p-Pcdha regulatory axis to EMT in metastatic progression of PCa. Targeting this newly identified regulatory axis provides a potential therapeutic strategy for aggressive PCa.

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Dysregulation of p53-RBM25-mediated circAMOTL1L biogenesis contributes to prostate cancer progression

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-08-27 | GSE113180 | GEO

human circRNA binding proteins in neuroblastoma

Project description:Circular RNAs (circRNAs), a noncoding RNA class originating from alternative splicing, are highly abundant in neural tissues and were shown to regulate gene expression e.g. by interacting with microRNAs and RNA-binding proteins. Neuroblastoma is an embryonal neoplasia, which arises from undifferentiated neural crest cells. Here, we aimed to explore, whether circRNAs influence the pathogenesis of high-risk neuroblastoma. We performed whole-transcriptome sequencing of 104 primary neuroblastoma samples of all risk-groups and identified 5,203 unique circRNAs involving 2,302 genes. Candidate circRNA expression did not correlate with host gene expression, indicating independent regulatory mechanisms. circRNAs were significantly downregulated in the MYCN-amplified high-risk tumors. These findings were independently reproduced in a tetracycline-inducible MYCN-overexpression system based on a non MYCN-amplified neuroblastoma cell line, suggesting that MYCN drives this global circRNA repression. We identified the RNA helicase DHX9 as a mediator of this global suppressive effect of MYCN on circRNAs. Comparing our RNA sequencing data with other cancers and controls revealed a circRNA subset specifically upregulated in neuroblastoma that included a circRNA derived from the ARID1A tumor suppressor gene. Specific circARID1A knockdown resulted in reduced proliferation, cell numbers and viability, prompted apoptosis and induced a differentiated phenotype. Neither knockdown, nor overexpression of circARID1A influenced ARID1A mRNA and protein levels significantly. To dissect the potential mode of function, we performed a pulldown assay with subsequent mass spectrometry. We identified the RNA-binding protein KHSRP as an interaction partner that participates in the mechanism of action of circARID1A. In summary, this study highlights an important role of circRNAs in neuroblastoma biology and may establish this RNA class as a future therapeutic target and biomarker.

2023-04-06 | PXD026053 | Pride

The FUS protein participates in circRNA biogenesis

Project description:The RNA binding protein FUS exerts its function in several RNA biosynthetic processes; moreover, mutations leading to changes in its expression levels or alterations in cellular compartmentalization have been linked to the pathogenesis of Amyotrophic Lateral Sclerosis. Here, we describe an additional novel function of FUS, that is the control of back-splicing reactions which lead to circular RNA (circRNA) production. We identified circRNAs expressed in murine ES-derived motoneurons and then compared their levels in control versus FUS-/- cells. We discovered that a considerable number of circRNAs is affected by FUS levels.

2017-02-27 | GSE83226 | GEO

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