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Long noncoding RNA LINC-PINT promotes proliferation through EZH2 and predicts poor prognosis in clear cell renal cell carcinoma

Authors Duan J, Ma X, Shi J, Xuan Y, Wang H, Li P, Zhang Y, Fan Y, Gong H, Ma X, Pang Y, Wang L, Yan Y, Zhang X

Received 25 January 2019

Accepted for publication 16 May 2019

Published 19 June 2019 Volume 2019:12 Pages 4729—4740

DOI https://doi.org/10.2147/OTT.S202938

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Ms Shreya Arora

Peer reviewer comments 2

Editor who approved publication: Dr Sanjeev Srivastava


Junyao Duan,1 Xin Ma,2 Jing Shi,1 Yundong Xuan,2 Hanfeng Wang,2 Pin Li,3 Yu Zhang,2 Yang Fan,2 Huijie Gong,1 Xuetao Ma,1 Yuewen Pang,1 Ling Wang,1 Yongji Yan,1 Xu Zhang2

1Department of Urology, Dongzhimen Hospital Affiliated to Beijing University of Chinese Medicine, Beijing 100700, People’s Republic of China; 2Department of Urology, State Key Laboratory of Kidney Diseases, PLA Medical School, Chinese People’s Liberation Army General Hospital, Beijing 100853, People’s Republic of China; 3School of Medicine, Nankai University, Tianjin 300071, People’s Republic of China

Background: Renal cell carcinoma (RCC) is one of the most common types of urological malignant tumors. Despite recent advances in diagnosis and management of RCC, its prognosis remains poor. Emerging evidence has shown that long noncoding RNAs (lncRNAs) play crucial regulatory roles in cancer biology.
Materials and methods: The most abundant transcript of long intergenic non-protein coding RNA p53 induced transcript (LINC-PINT) in clear cell RCC (ccRCC) was determined by RT-PCR. Quantitative real-time PCR was performed to examine LINC-PINT expression in paired ccRCC samples and cell lines. The relationship of LINC-PINT expression with clinicopathologic characteristics and clinical outcome was analyzed. The biological function of LINC-PINT was studied by MTS and colony formation. The flow cytometry was used to analyze cell cycle distribution and apoptosis. The subcelluar fractionation and RIP assay was performed to explore the molecular mechanism of LINC-PINT. Western blotting and immunofluorescence was carried out to examine EZH2 and p53.
Results: We found that the LINC-PINT was frequently upregulated in ccRCC samples. Furthermore, we observed that the level of LINC-PINT depended on gender as well as on pT and TNM stage of patients with ccRCC. Moreover, patients with high LINC-PINT expression had poor disease-free survival and overall survival. Functionally, overexpression of LINC-PINT promoted ccRCC cell proliferation, induced cell cycle progression, and inhibited apoptosis. LINC-PINT was primarily located in cell nuclei and interacted with EZH2. When EZH2 was knocked down in 769P and OS-RC-2 cells overexpressing LINC-PINT, the effect of LINC-PINT on cell proliferation, cell cycle, and apoptosis was partially reversed. Additionally, inducing p53 by doxorubicin (Dox) promoted LINC-PINT expression.
Conclusion: Collectively, our results provide novel insights into the important role of LINC-PINT in ccRCC development and indicate that LINC-PINT may serve as a valuable prognostic biomarker for ccRCC.

Keywords: long noncoding RNA, LINC-PINT, clear cell renal cell carcinoma, prognosis, cell proliferation, EZH2

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