Abstract
BackgroundProstate 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.MethodsThe 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.ResultsLINC00261, 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.ConclusionsOur study demonstrates the inhibitory role of LINC00261 in prostate cancer progression, providing a novel biomarker for early detection of prostate cancer.
Highlights
Prostate cancer is one of the leading causes of cancer death in males
The significance of LINC00261 in prostate cancer The gene expression dataset GSE45016 was downloaded from the Gene Expression Omnibus (GEO) database, and 667 prostate cancer-related differentially expressed genes (DEGs) were obtained by differential analysis, of which 329 were highly expressed and 338 poorly expressed genes (Fig. 1a)
Validation with Gene Expression Profiling Interactive Analysis (GEPIA) database revealed that Dickkopf-related protein 3 (DKK3) expression was decreased in prostate cancer (Fig. 1f ), which further demonstrated that LINC00261 might regulate DKK3 by binding to transcription factor GATA binding protein 6 (GATA6), affecting the development of prostate cancer
Summary
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. Prostate cancer is a life-threatening malignancy for men with approximately 1.3 million new cases and 359,000 deaths occurred in 2018 [1]. The early detection of prostate cancer was improved by prostate-specific antigen (PSA), As a class of transcripts, lncRNAs are involved in various biological processes [5]. 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 HOTAIR is involved in prostate cancer cell biological functions [6].
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