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

• Published in: OncoTargets and therapy Vol. 12; pp. 4729 - 4740
• Main Authors: Duan, Junyao, Ma, Xin, Shi, Jing, Xuan, Yundong, Wang, Hanfeng, Li, Pin, Zhang, Yu, Fan, Yang, Gong, Huijie, Ma, Xuetao, Pang, Yuewen, Wang, Ling, Yan, Yongji, Zhang, Xu
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.06.2019; Dove; Dove Medical Press
• Subjects: Anthracyclines; Antisense RNA; apoptosis; Cancer; Carcinoma; Cell cycle; cell proliferation; clear cell renal cell carcinoma; Development and progression; EZH2; Fluorescent antibody technique; LINC-PINT; long noncoding RNA; Novels; Original Research; prognosis; Renal cell carcinoma; RNA; Sunitinib; Tumor proteins; Tumors; China; long noncoding RNA; clear cell renal cell carcinoma; LINC-PINT; cell proliferation; prognosis; EZH2
• ISSN: 1178-6930; 1178-6930
• DOI: 10.2147/OTT.S202938

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. The most abundant transcript of long intergenic non-protein coding RNA p53 induced transcript ( ) in clear cell RCC (ccRCC) was determined by RT-PCR. Quantitative real-time PCR was performed to examine expression in paired ccRCC samples and cell lines. The relationship of expression with clinicopathologic characteristics and clinical outcome was analyzed. The biological function of 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 Western blotting and immunofluorescence was carried out to examine EZH2 and p53. We found that the was frequently upregulated in ccRCC samples. Furthermore, we observed that the level of depended on gender as well as on pT and TNM stage of patients with ccRCC. Moreover, patients with high expression had poor disease-free survival and overall survival. Functionally, overexpression of promoted ccRCC cell proliferation, induced cell cycle progression, and inhibited apoptosis. was primarily located in cell nuclei and interacted with EZH2. When EZH2 was knocked down in 769P and OS-RC-2 cells overexpressing , the effect of on cell proliferation, cell cycle, and apoptosis was partially reversed. Additionally, inducing p53 by doxorubicin (Dox) promoted expression. Collectively, our results provide novel insights into the important role of in ccRCC development and indicate that may serve as a valuable prognostic biomarker for ccRCC.