A novel LncRNA transcript, RBAT1, accelerates tumorigenesis through interacting with HNRNPL and cis-activating E2F3
Posted on 2020-07-16 - 04:38
Abstract 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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He, Xiaoyu; Chai, Peiwei; Li, Fang; Zhang, Leilei; Zhou, Chuandi; Yuan, Xiaoling; et al. (2020). A novel LncRNA transcript, RBAT1, accelerates tumorigenesis through interacting with HNRNPL and cis-activating E2F3. figshare. Collection. https://doi.org/10.6084/m9.figshare.c.5063855.v1
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AUTHORS (13)
XH
Xiaoyu He
PC
Peiwei Chai
FL
Fang Li
LZ
Leilei Zhang
CZ
Chuandi Zhou
XY
Xiaoling Yuan
YL
Yongyun Li
JY
Jie Yang
YL
Yingxiu Luo
SG
Shengfang Ge
HZ
He Zhang
RJ
Renbing Jia
XF
Xianqun Fan
CATEGORIES
KEYWORDS
RBAT 1-interacting proteinsMethods RBAT 1 expressionE 2F promoterlncRNAPCRRBAT 1 expressionGapmeR-mediated RBAT 1novel LncRNA transcriptcis-activating E 2F Abstract Backgr...HNRNPLorthotopic xenograft retinoblastoma...PDXRBAT 1Conclusions RBAT 1 overexpression u...HNPNPLE 2F transcriptiontumorigenesiRBAT 1-targeting GapmeRsRb cell lines