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RETINOBLASTOMA MICRORNA LANDSCAPE

ABSTRACT: In this work we examined miRNome expression in 12 samples of retinoblastoma. Present miRNAs show the common working machinery with Rb affecting most of pathways considered hallmarks of cancer.

ORGANISM(S): synthetic construct Homo sapiens

PROVIDER: GSE84747 | GEO | 2017/07/10

SECONDARY ACCESSION(S): PRJNA331160

REPOSITORIES: GEO

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Plasma miRNome analysis from retinoblastoma patients reveals the size of the circulating miRNome, a tumor signature and new normalizers candidates.

Project description:In This work we analyzed the mirnome in plasma and corresponding extracellular vesicles (EVs) from 12 patients affected by retinoblastoma (Rb) a childhood intraocular malignant tumor, as well as from 12 healthy aged matched controls. Using hierarchical clustering with the detection score microarrays provide for each miRNA and we identified a plasma signature of 19 miRNAs in all Rb cases that were able to discriminate both cases from controls.

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MicroRNA profiling by arrray of unilaterial and bilateral retinoblastoma tumours from enucleated patients with no chemotherapy history

Project description:Retinoblastoma (Rb) is the most common intraocular tumor in childhood and represent a very robust model about hereditary develop for cancer. We believe that miRNome expression may give clues to understanding Rb heterogeneity and to comprehend biological features in order to find new biomarkers for better treatments. We explore 12 Rb tumors from enucleated patients with no chemotherapy history from Children Hospital of Mexico Federico Gomez and Pediatric Hospital Medical Center XXI century by informed parental consent to collaborate with retrospective research. 5 bilateral and 7 unilateral, 4 female and 8 male samples were tailed and labeled with biotin to hybridize in GeneChip miRNA 4.0 Affymetrix array. Chips were washed and scanned 18hrs after hybridization.

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Proteomic Profiling of Retinoblastoma-Derived Exosomes reveals potential biomarkers of vitreous seeding

Project description:Retinoblastoma (RB) is the most common tumor of the eye in early childhood. Despite recent advances in conservative treatment have greatly improved the visual outcome, local tumor control remain difficult in presence of massive vitreous seeding. Traditional biopsy has long been considered unsafe in RB, due to the risk of extraocular spread. Thus, the identification of new biomarkers is crucial to design safer diagnostic and more effective therapeutic approaches. Exosomes represent an interesting alternative to detect tumor-associated biomarkers. In this study we defined the protein signature of exosomes released by RB tumors (RBT) and vitreous seeding (RBVS) primary cell lines by high resolution mass spectrometry. A total of 5666 proteins were identified. Among these, 5223 and 3637 were expressed in exosome RBT and one RBVS group respectively.

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Differential microRNA expression profiles in Retinoblastoma serum

Project description:Retinoblastoma (RB) is a malignant intraocular neoplasm occurs mostly in children. The malignancy caused due to altered miRNA expression in cancer tumors and circulating body fluids has been reported in several cancers. The aberrantly expressed microRNAs are useful for diagnosis and prognosticating the tumors. Circulating miRNAs have been identified as potential markers in neoplastic and non -neoplastic diseases. The aim of the study involves identifying microRNA signatures of serum of Retinoblastoma and possible use of differential miRNA as unique biomarker for RB. Agilent Single Color Whole miRNA microarray: 14 advanced stage Retinoblastoma Serum (pooled) Vs 14 Non-Retinoblastoma Serum (pooled) samples

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Project description:Retinoblastoma (RB) is the most prevalent ocular tumor of childhood whose extraocular invasion largely increase metastasis risk. Nevertheless, a single-cell characterization of RB local extension has been lacking. Here, we perform single-cell RNA sequencing (scRNA-seq) 4 RB samples (2 from intraocular and 2 from extraocular RB patients), and integrate public scRNA-seq datasets to characterize the local extension of RB at single-cell level.

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Project description:The main objective of the study is to identify the de-regulated miRNAs in association with HMGA2 (oncogene) in the Retinoblastoma tumorus. The present experiment was carried out using Y79 (Retinoblastoma cell line), as the invitro model of Retinoblastoma tumor. The HMGA2 transcripts were silenced using siRNA and the post-silenced RB cells (at the end of 48 hours) were subjected to miRNA profiling using agilent platform.The key miRNAs de-regulated in this experiment has been validated using qRT-PCR and further their role has been evaluated by addition of specific antagomirs in RB cell lines (Y79 and Weri Rb 1).

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Differential expression of miRNAs in Retinoblastoma cells (Y79) in response to anti-HMGA2 siRNA treatment

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Human embryonic stem cell-derived organoidal retinoblastoma reveals cancerous origin and therapeutic target

Project description:Retinoblastoma (Rb) is the most prevalent intraocular malignant tumor in children with less than 30% survival rate globally. Rb genetic predisposition has been well defined for decades, whereas its developmental origin and drug agents remain largely unexplored. Here we developed the first organoidal retinoblastoma model derived from human embryonic stem cells (hESCs) with a biallelic knockout (RB1-/-) or mutagenesis (RB1Mut/Mut) of the RB1 gene, which exhibit extreme consistent properties of Rb tumorigenesis, transcriptome, and genome-wide methylation. Using single-cell RNA-seq and immunostaining of this model, we found that developmentally Rb originated from ARR3+ maturing cone precursors and a new cell type of unfolded protein response occurred in the organoidal retinoblastoma. A key PI3K-Akt pathway was aberrantly regulated, and its strong activator SYK (encoding proto-oncogenic spleen tyrosine kinase) was significantly upregulated in the cancerous organoids. Furthermore, we demonstrated that the SYK inhibitors, A502 and B502, have more significant therapeutic response on the early-stage organoidal retinoblastoma compared to four well-established chemotherapeutic drugs in clinic. Collectively, we established a brand-new organoidal retinoblastoma model derived from human ESCs in-a-dish and discovered its cell-of-origin and potential drug agents, shedding light on development and therapeutics of human cancers.

2020-09-05 | GSE136929 | GEO

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