A novel LncRNA transcript, RBAT1, accelerates tumorigenesis through interacting with HNRNPL and cis-activating E2F3
Autor: | Shengfang Ge, Chuandi Zhou, Xianqun Fan, Renbing Jia, Peiwei Chai, Fang Li, Yongyun Li, Leilei Zhang, Yingxiu Luo, Xiaoyu He, He Zhang, Xiaoling Yuan, Jie Yang |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Cancer Research Biology medicine.disease_cause Models Biological lcsh:RC254-282 Mice 03 medical and health sciences 0302 clinical medicine Transcription (biology) Cell Line Tumor medicine Animals Humans Gene silencing Gene Silencing Epigenetics Promoter Regions Genetic Oncogene Retinoblastoma Research lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease Immunohistochemistry Xenograft Model Antitumor Assays Chromatin Disease Models Animal Cell Transformation Neoplastic 030104 developmental biology Gene Expression Regulation Ribonucleoproteins Urinary Bladder Neoplasms Oncology E2F3 Transcription Factor 030220 oncology & carcinogenesis Cancer research Molecular Medicine RNA Interference RNA Long Noncoding RNA extraction Carcinogenesis Protein Binding Signal Transduction |
Zdroj: | Molecular Cancer, Vol 19, Iss 1, Pp 1-20 (2020) Molecular Cancer |
ISSN: | 1476-4598 |
Popis: | BackgroundLong 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.MethodsRBAT1 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.ResultsHere, 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.ConclusionsRBAT1 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. |
Databáze: | OpenAIRE |
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