已发表论文

长链非编码 RNA LINC-PINT  通过 EZH2 促进增殖,并预测透明细胞肾细胞癌的预后不良

 

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

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




Figure 3 LINC-PINT promotes ccRCC cell proliferation...