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Title:
A novel LncRNA transcript, RBAT1, accelerates tumorigenesis through interacting with HNRNPL and cis-activating E2F3 | Molecular Cancer
Description:
Background Long non-coding RNAs (lncRNAs) have been identified as important epigenetic regulators that play critical roles in human cancers. However, the regulatory functions of lncRNAs in tumorigenesis remains to be elucidated. Here, we aimed to investigate the molecular mechanisms and potential clinical application of a novel lncRNA, retinoblastoma associated transcript-1 (RBAT1), in tumorigenesis. Methods RBAT1 expression was determined by real-time PCR in both retinoblastoma (Rb) and bladder cancer (BCa) cell lines and clinical tissues. Chromatin isolation using RNA purification (ChIRP) assays were performed to identify RBAT1-interacting proteins. Patient-derived xenograft (PDX) retinoblastoma models were established to test the therapeutic potential of RBAT1-targeting GapmeRs. Results Here, we found that RBAT1 expression was significantly higher in Rb and BCa tissues than that in adjacent tissues. Functional assays revealed that RBAT1 accelerated tumorigenesis both in vitro and in vivo. Mechanistically, RBAT1 recruited HNRNPL protein to E2F3 promoter, thereby activating E2F3 transcription. Therapeutically, GapmeR-mediated RBAT1 silencing significantly inhibited tumorigenesis in orthotopic xenograft retinoblastoma models derived from Rb cell lines and Rb primary cells. Conclusions RBAT1 overexpression upregulates a known oncogene, E2F3, via directly recruiting HNPNPL to its promoter and cis-activating its expression. Our finding provides a novel mechanism of lncRNA biology and provides potential targets for diagnosis and treatment of Rb and BCa.
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Keywords {š}
rbat, cell, fig, expression, pubmed, lines, tumor, cancer, rna, cells, google, scholar, supplementary, promoter, hnrnpl, cas, retinoblastoma, bca, lncrna, analysis, gapmer, performed, gene, genes, noncoding, control, tissues, lncrnas, bladder, central, data, region, protein, proliferation, werirb, assays, number, pcr, results, formation, long, realtime, tumors, showed, table, potential, significantly, transcription, silencing, assay,
Topics {āļø}
mir-106a-5p/e2f3 axis y-axis represents log g0/g1 phase increased noncoding rna revolution-trashing poly-l-lysine-coated 6 rna-directed proteomic discovery real-time pcr showing stage ii/iii/iv anti-rna polymerase-ii real-time pcr showed rnase-h-mediated degradation liver tumour-initiating cells article download pdf shrna-expressing plasmid construction streptavidin-conjugated magnet beads lna-modified antisense oligonucleotides nuclear/cytosol fractionation kit axis represents log primescript rt-pcr kit real-time qpcr analysis alternative splicing events real-time pcr analysis cell cycle-dependent expression nf-kb signaling pathway kaplan-meier survival analysis stat3-mediated sox4 expression wild-type rb protein triple-negative breast cancer firefly/renilla luciferase assays rbat1-induced e2f3 activation e2f3-silencing significantly reduced seventeen chirp-purified proteins blue points denote real-time pcr confirmed intestinal epithelial differentiation understanding rna-chromatin interactions lncrna-rbat/hnrnpl complex tcf7-targeted shrna resulted gene expression profiles coding rna sammson e2f3-overexpressing cell lines red points denote regulates cell growth scientific research program sv-huc-1 cell lines identify rbat1-interacting proteins e2f3-overexpressed cell lines gapmer-mediated silencing privacy choices/manage cookies long noncoding rnas
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headline:A novel LncRNA transcript, RBAT1, accelerates tumorigenesis through interacting with HNRNPL and cis-activating E2F3
description:Long non-coding RNAs (lncRNAs) have been identified as important epigenetic regulators that play critical roles in human cancers. However, the regulatory functions of lncRNAs in tumorigenesis remains to be elucidated. Here, we aimed to investigate the molecular mechanisms and potential clinical application of a novel lncRNA, retinoblastoma associated transcript-1 (RBAT1), in tumorigenesis. RBAT1 expression was determined by real-time PCR in both retinoblastoma (Rb) and bladder cancer (BCa) cell lines and clinical tissues. Chromatin isolation using RNA purification (ChIRP) assays were performed to identify RBAT1-interacting proteins. Patient-derived xenograft (PDX) retinoblastoma models were established to test the therapeutic potential of RBAT1-targeting GapmeRs. Here, we found that RBAT1 expression was significantly higher in Rb and BCa tissues than that in adjacent tissues. Functional assays revealed that RBAT1 accelerated tumorigenesis both in vitro and in vivo. Mechanistically, RBAT1 recruited HNRNPL protein to E2F3 promoter, thereby activating E2F3 transcription. Therapeutically, GapmeR-mediated RBAT1 silencing significantly inhibited tumorigenesis in orthotopic xenograft retinoblastoma models derived from Rb cell lines and Rb primary cells. RBAT1 overexpression upregulates a known oncogene, E2F3, via directly recruiting HNPNPL to its promoter and cis-activating its expression. Our finding provides a novel mechanism of lncRNA biology and provides potential targets for diagnosis and treatment of Rb and BCa.
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description:Long non-coding RNAs (lncRNAs) have been identified as important epigenetic regulators that play critical roles in human cancers. However, the regulatory functions of lncRNAs in tumorigenesis remains to be elucidated. Here, we aimed to investigate the molecular mechanisms and potential clinical application of a novel lncRNA, retinoblastoma associated transcript-1 (RBAT1), in tumorigenesis. RBAT1 expression was determined by real-time PCR in both retinoblastoma (Rb) and bladder cancer (BCa) cell lines and clinical tissues. Chromatin isolation using RNA purification (ChIRP) assays were performed to identify RBAT1-interacting proteins. Patient-derived xenograft (PDX) retinoblastoma models were established to test the therapeutic potential of RBAT1-targeting GapmeRs. Here, we found that RBAT1 expression was significantly higher in Rb and BCa tissues than that in adjacent tissues. Functional assays revealed that RBAT1 accelerated tumorigenesis both in vitro and in vivo. Mechanistically, RBAT1 recruited HNRNPL protein to E2F3 promoter, thereby activating E2F3 transcription. Therapeutically, GapmeR-mediated RBAT1 silencing significantly inhibited tumorigenesis in orthotopic xenograft retinoblastoma models derived from Rb cell lines and Rb primary cells. RBAT1 overexpression upregulates a known oncogene, E2F3, via directly recruiting HNPNPL to its promoter and cis-activating its expression. Our finding provides a novel mechanism of lncRNA biology and provides potential targets for diagnosis and treatment of Rb and BCa.
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address:
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address:
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email:[email protected]
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type:PostalAddress
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address:
name:Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
type:PostalAddress
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email:[email protected]
name:Xianqun Fan
affiliation:
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address:
name:Department of Ophthalmology, Ninth Peopleās Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
type:PostalAddress
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address:
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email:[email protected]
PostalAddress:
name:Department of Ophthalmology, Ninth Peopleās Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
name:Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
name:Department of Ophthalmology, Ninth Peopleās Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
name:Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
name:Department of Ophthalmology, Ninth Peopleās Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
name:Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
name:Department of Ophthalmology, Ninth Peopleās Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
name:Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
name:Department of Ophthalmology, Ninth Peopleās Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
name:Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
name:Department of Ophthalmology, Ninth Peopleās Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
name:Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
name:Department of Ophthalmology, Ninth Peopleās Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
name:Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
name:Department of Ophthalmology, Ninth Peopleās Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
name:Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
name:Department of Ophthalmology, Ninth Peopleās Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
name:Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
name:Department of Ophthalmology, Ninth Peopleās Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
name:Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
name:Department of Ophthalmology, Ninth Peopleās Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
name:Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
name:Department of Ophthalmology, Ninth Peopleās Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
name:Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
name:Department of Ophthalmology, Ninth Peopleās Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China
name:Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China
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