Long noncoding RNA LINC00261 suppresses prostate cancer tumorigenesis through upregulation of GATA6-mediated DKK3
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PRIMARY RESEARCH
Cancer Cell International Open Access
Long noncoding RNA LINC00261 suppresses prostate cancer tumorigenesis through upregulation of GATA6-mediated DKK3 Yang Li, Hai Li and Xin Wei*
Abstract Background: Prostate cancer is one of the leading causes of cancer death in males. Recent studies have reported aberrant expression of lncRNAs in prostate cancer. This study explores the role of LINC00261 in prostate cancer progression. Methods: The differentially expressed genes, transcription factors, and lncRNAs related to prostate cancer were predicted by bioinformatics analysis. Prostate cancer tissue samples and cell lines were collected for the determination of the expression of LINC00261 by reverse transcription quantitative polymerase chain reaction. The binding capacity of LINC00261 to the transcription factor GATA6 was detected by RIP, and GATA6 binding to the DKK3 promoter region was assessed by ChIP. In addition, luciferase reporter system was used to verify whether LINC00261 was present at the DKK3 promoter. After gain- and loss-of function approaches, the effect of LINC00261 on prostate cancer in vitro and in vivo was assessed by the determination of cell proliferation, invasion and migration as well as angiogenesis. Results: LINC00261, GATA6, and DKK3 were poorly expressed in prostate cancer. LINC00261 could inhibit transcriptional expression of DKK3 by recruiting GATA6. Overexpression of LINC00261 inhibited prostate cancer cells proliferation, migration, and invasion as well as angiogenesis, which could be reversed by silencing DKK3. Furthermore, LINC00261 could also suppress the tumorigenicity of cancer cells in vivo. Conclusions: Our study demonstrates the inhibitory role of LINC00261 in prostate cancer progression, providing a novel biomarker for early detection of prostate cancer. Keywords: Prostate cancer, Long noncoding RNA LINC00261, GATA binding protein 6, Dickkopf-related protein 3 Background Prostate cancer is a life-threatening malignancy for men with approximately 1.3 million new cases and 359,000 deaths occurred in 2018 [1]. Of note, prostate cancer is more common in developed countries than developing countries, the former also having a higher mortality rate [2]. In the past decade, the early detection of prostate cancer was improved by prostate-specific antigen (PSA), *Correspondence: [email protected] Department of Urology, China-Japan Union Hospital of Jilin University, No. 126, Xiantai Street, Changchun 130033, Jilin, People’s Republic of China
which is reflected by increased detection rate of localized tumors [3]. Aberrant expression of long noncoding RNAs (lncRNAs) plays an essential role in cancer progressions [4]. As a class of transcripts, lncRNAs are involved in various biological processes [5]. LncRNAs are often dysregulated when faced with disturbance of cellular function. Therefore, lncRNAs can be used as early markers for disease detection. A recent report showed that lncRNA HOTAIR expression was increased in castration-resistant prostate cancer cells, and
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