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
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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