Hypoxia-regulated lncRNA CRPAT4 promotes cell migration via regulating AVL9 in clear cell renal cell carcinomas
Received 24 March 2018
Accepted for publication 23 May 2018
Published 3 August 2018 Volume 2018:11 Pages 4537—4545
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Amy Norman
Peer reviewer comments 2
Editor who approved publication: Prof. Dr. Geoffrey Pietersz
Wenhua Zhang,1,* Jue Wang,2,* Rong Chai,3 Guangxin Zhong,1 Cong Zhang,1 Wenjia Cao,4 Lei Yan,1 Xiang Zhang,1 Zhonghua Xu1
1Department of Urology, Qilu Hospital of Shandong University, Jinan, People’s Republic of China; 2Central Laboratory, The Second Hospital of Shandong University, Jinan, People’s Republic of China; 3Department of First Operating Room, Qilu Hospital of Shandong University, Jinan, People’s Republic of China; 4Department of Oncology, Shandong Cancer Hospital and Institute, Jinan, People’s Republic of China
*These authors contributed equally to this work
Introduction: Long noncoding RNAs (lncRNAs) are proven to be key regulators in cancer biology. Our screening effort for clear cell renal cell carcinoma (ccRCC) prognosis-associated lncRNAs identified a novel lncRNA, ccRCC prognosis-associated transcript 4 (CRPAT4), as one of the top candidates that was previously uncharacterized. The aim of this study was to verify the clinical significance of CRPAT4 in ccRCC patients and to explore its biological role as well as the underlying mechanisms, in ccRCC cell lines.
Materials and methods: Quantitative real-time polymerase chain reaction (PCR) was performed to demonstrate that CRPAT4 was differentially expressed between ccRCC and the normal controls and that high CRPAT4 expression significantly associated with advanced Fuhrman nuclear grades.
Results: Kaplan–Meier survival analysis with The Cancer Genome Atlas KIRC RNA sequencing data indicated that high CRPAT4 expression was significantly associated with poor overall survival and progression-free survival. Functional studies indicated that CRPAT4 was an HIF-1α regulated gene, and CRPAT4 knockdown significantly inhibited cell migration and proliferation in the absence of HIF-1α. In addition, a mechanistic study revealed that CRPAT4 could regulate the expression of the migration-associated protein AVL9.
Conclusion: Collectively, our study first identified CRPAT4 as a hypoxia-regulated lncRNA, acting as an oncogene in ccRCC progression via regulating AVL9 protein, thus expanding our knowledge on the hypoxia pathway in ccRCC biology from a noncoding perspective. Moreover, CRPAT4 has the potential to be a prognostic marker in ccRCC patients.
Keywords: CRPAT4, AVL9, hypoxia, clear cell renal cell carcinoma, migration
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