Lincrna-ror is activated by h3k27 acetylation and induces emt in retinoblastoma by acting as a sponge of mir-32 to activate the notch signaling pathway

Lincrna-ror is activated by h3k27 acetylation and induces emt in retinoblastoma by acting as a sponge of mir-32 to activate the notch signaling pathway

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ABSTRACT Recent studies have suggested that lincRNA-ROR is involved in the tumorigenesis of different types of cancers. However, the role of lincRNA-ROR in retinoblastoma has not been


determined. We investigated lincRNA-ROR levels in 58 retinoblastoma and adjacent non-tumor tissues by quantitative reverse transcription PCR. Recurrence-free survival was analyzed using Cox


regression analyses. Cell migration and invasion abilities were detected by wound-healing, Transwell invasion, and bioluminescence imaging assays. Western blotting was performed to detect


epithelial–mesenchymal transition markers. Interactions between lincRNA-ROR, miR-32-5p, and Notch1 were confirmed by Luciferase, RNA pull-down, and RIP assays. Histone acetylation was


detected by chromatin immunoprecipitation assays. We showed that lincRNA-ROR was significantly upregulated in retinoblastoma tissues, and overexpression of lincRNA-ROR was significantly


correlated with optic nerve invasion, nodal or distant metastasis, and recurrence. We also showed that lincRNA-ROR is a critical promoter of retinoblastoma cell metastasis, both in vivo and


in vitro. Further, we demonstrated that lincRNA-ROR activates the Notch signaling pathway by acting as a sponge of miR-32-5p. Upregulation of lincRNA-ROR was attributed to the CBP-mediated


H3K27 acetylation at the promoter region. Our results reveal a potential competing endogenous RNA regulatory pathway, in which lincRNA-ROR modulates the epithelial–mesenchymal transition


program by competitively binding to endogenous miR-32-5p and regulating Notch signaling pathway activity in retinoblastoma cells, which may provide new insights into novel molecular


therapeutic targets for retinoblastoma. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through


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squamous cell carcinoma. Int J Oncol. 2019;54:1183–94. CAS  PubMed  PubMed Central  Google Scholar  Download references FUNDING The Project Supported by Shenzhen Science and Technology Plan


Project (Grant no. JCYJ20170307095222274), Natural Science Foundation of Guangdong Province (Grant no. 2019A1515010412), National Natural Science Foundation of China (Grant no. 81902751).


AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Ophthalmology, The Second Clinical Medical College (Shenzhen People’s Hospital), Jinan University, Shenzhen, China Yali Gao & 


Xiaoling Luo * Department of Obstetrics and Gynecology, The Second Clinical Medical College (Shenzhen People’s Hospital), Jinan University, Shenzhen, China Jun Zhang Authors * Yali Gao View


author publications You can also search for this author inPubMed Google Scholar * Xiaoling Luo View author publications You can also search for this author inPubMed Google Scholar * Jun


Zhang View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Jun Zhang. ETHICS DECLARATIONS CONFLICT OF INTEREST The


authors declare that they have no conflict of interest. ETHICS STATEMENT All procedures performed in studies involving human participants and animals were in accordance with the ethical


standards of the ethic committee of the Shenzhen People’s Hospital. ADDITIONAL INFORMATION PUBLISHER’S NOTE Springer Nature remains neutral with regard to jurisdictional claims in published


maps and institutional affiliations. SUPPLEMENTARY INFORMATION TABLE S1 TABLE S2 RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Gao, Y., Luo, X. &


Zhang, J. LincRNA-ROR is activated by H3K27 acetylation and induces EMT in retinoblastoma by acting as a sponge of miR-32 to activate the Notch signaling pathway. _Cancer Gene Ther_ 28,


42–54 (2021). https://doi.org/10.1038/s41417-020-0181-z Download citation * Received: 23 February 2020 * Revised: 06 May 2020 * Accepted: 07 May 2020 * Published: 22 May 2020 * Issue Date:


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