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ABSTRACT Current reports refer to the role of long noncoding RNA (lncRNA) prostate androgen-regulated transcript 1 (PART1) as a tumor suppressor in some types of cancer but as an oncogene in

other kinds of cancer. In gastric cancer, it had been reported to be downregulated. However, the clinical significance and underlying mechanism of PART1 function in gastric cancer remains

undefined. Here, seven differential expression levels of noncoding RNAs (DE-lncRNAs) were screened from gastric cancer through a probe reannotation of a human exon array. PART1 was selected

for further study because of its high fold change number. In our cohort, PART1 was identified as a significant downregulated lncRNA in gastric cancer tissues by qPCR and in situ

hybridization (ISH), and its low expression was significantly correlated with postoperative metastasis and short overall survival time after surgery. Through the results of gain-of-function

experiments, PART1 was confirmed as a tumor suppressor that can decrease not only cell viability, migration, and invasion in vitro but also tumorigenesis and tumor metastasis in vivo.

Mechanistically, RNA pull-down and RNA-binding protein immunoprecipitation (RIP) showed that PART1 interacts with androgen receptor (AR), and then, promyelocytic leukemia zinc finger (PLZF)

is upregulated in an androgen-independent manner. In a chain reaction, chromatin immunoprecipitation (ChIP) assay additionally illustrated that PLZF upregulation increased the enrichment of

EZH2 and H3K27 trimethylation in the platelet-derived growth factor (PDGFB) promotor, thereby inhibition of PDGFB and the subsequent PDGFRβ/PI3K/Akt signaling pathway. Based on these

findings, we showed PART1 plays a tumor suppressor role _by_ promoting PLZF expression followed by recruitment of EZH2 to mediate epigenetic PDGFB silencing and downstream PI3K/Akt

inhibition, suggesting that PART1 has a key role in restraining the aggressive ability of GC cells and providing a novel perspective on lncRNAs in GC progression. Access through your

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BEING VIEWED BY OTHERS AR AND ERG DRIVE THE EXPRESSION OF PROSTATE CANCER SPECIFIC LONG NONCODING RNAS Article 17 June 2020 LNCRNA _SNHG1_ AND RNA BINDING PROTEIN _HNRNPL_ FORM A COMPLEX AND

COREGULATE _CDH1_ TO BOOST THE GROWTH AND METASTASIS OF PROSTATE CANCER Article Open access 01 February 2021 LNCRNA LINC00667 AGGRAVATES THE PROGRESSION OF HEPATOCELLULAR CARCINOMA BY

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2013;19:3658–64. CAS  PubMed  PubMed Central  Google Scholar  Download references FUNDING This work was supported by grants from the National Natural Science Foundation of China (81772632,

81802943), Science Foundation of Peking University Cancer Hospital 2020-9, Beijing outstanding talent training program (No. 2018000021469G268), the interdisciplinary medicine Seed Fund of

Peking University (No. BMU2018MX019), Special funds of the Ministry of Finance for Reform and Development and ‘San Ming’ Project of Shenzhen city (no. SZSM 201612051). AUTHOR INFORMATION

Author notes * These authors contributed equally: S. Wang, J. Meng, G. Lyu, G. Ding AUTHORS AND AFFILIATIONS * Department of Biobank, Key laboratory of Carcinogenesis and Translational

Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Beijing, P.R. China H. Han, G. Ding & Y. Hu * Department of Clinical Laboratory, Peking

University Cancer Hospital & Institute, Beijing, P.R. China S. Wang, J. Meng, L. Wang, W. Yang & Y. Lv * Department of Gastrointestinal Surgery, Peking University Shenzhen Hospital,

Shenzhen, P.R. China G. Lyu * Department of Central Laboratory, Peking University Cancer Hospital & Institute, Beijing, P.R. China L. Wu * Department of Molecular Diagnostics, Peking

University Cancer Hospital & Institute, Beijing, P.R. China S. Jia * Department of Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, Beijing, P.R. China L.

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CITE THIS ARTICLE Han, H., Wang, S., Meng, J. _et al._ Long noncoding RNA PART1 restrains aggressive gastric cancer through the epigenetic silencing of PDGFB _via_ the PLZF-mediated

recruitment of EZH2. _Oncogene_ 39, 6513–6528 (2020). https://doi.org/10.1038/s41388-020-01442-5 Download citation * Received: 14 February 2020 * Revised: 19 July 2020 * Accepted: 21 August

2020 * Published: 08 September 2020 * Issue Date: 15 October 2020 * DOI: https://doi.org/10.1038/s41388-020-01442-5 SHARE THIS ARTICLE Anyone you share the following link with will be able

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