Abstract
BackgroundAccumulating evidence has associated aberrant long non-coding RNAs (lncRNAs) with various human cancers. This study aimed to explore the role of LINC00908 in prostate cancer (PCa) and its possible underlying mechanisms.MethodsMicroarray data associated with PCa were obtained from the Gene Expression Omnibus (GEO) to screen the differentially expressed genes or lncRNAs. Then, the expression of LINC00908 in PCa tissues and cell lines was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The localization of LINC00908 in PCa cells was examined by fluorescence in situ hybridization (FISH). The relationship among LINC00908, microRNA (miR)-483-5p, and TSPYL5 was detected by bioinformatics analysis, dual-luciferase reporter assay, RNA pull-down, RNA binding protein immunoprecipitation (RIP), and FISH assays. Cell biological behaviors were assessed after the expression of LINC00908, miR-483-5p, and TSPYL5 was altered in PCa cells. Lastly, tumor growth in nude mice was evaluated.ResultsPoorly expressed LINC00908 was witnessed in PCa tissues and cells. LINC00908 competitively bound to miR-483-5p to up-regulate the TSPYL5 expression. Overexpression of LINC00908 resulted in reduced PCa cell proliferation, migration and invasion, and promoted apoptosis. Additionally, the suppression on PCa cell proliferation, migration and invasion was induced by up-regulation of TSPYL5 or inhibition of miR-483-5p. In addition, in vivo experiments showed that overexpression of LINC00908 inhibited tumor growth of PCa.ConclusionOverall, LINC00908 could competitively bind to miR-483-5p to increase the expression of TSPYL5, thereby inhibiting the progression of PCa. Therefore, LINC00908 may serve as a novel target for the treatment of PCa.
Highlights
Accumulating evidence has associated aberrant long non-coding RNAs with various human cancers
LINC00908 is poorly expressed in prostate cancer (PCa) tissues and cell lines Firstly, differential analyses were performed on PCa-associated microarray datasets GSE3325 and GSE69223 (Fig. 1a, b) obtained from the Gene Expression Omnibus (GEO) database and GEPIA database (Fig. 1c), which revealed that LINC00908 was significantly down-regulated a b c d e f g
Overexpression of LINC00908 inhibits PCa cell proliferation, migration, and invasion while inducing apoptosis Having identified the low expression of LINC00908 in PCa, we focused on the role of LINC00908 in the biological functions of PCa cells
Summary
Accumulating evidence has associated aberrant long non-coding RNAs (lncRNAs) with various human cancers. The overexpression of lncRNA growth arrest-specific transcript 5 (GAS5) has been previously demonstrated to suppress cell migration and invasion in PCa [10]. Based on the web-available microarrays prior to our study, LINC00908 has been revealed to be significantly down-regulated in PCa. it has been demonstrated that lncRNAs may possess the ability to antagonize the post-transcriptional regulation of microRNAs (miRNAs or miRs) in the expression of genes, playing a vital role in human disease development [11]. Another study demonstrated that downregulation of miR-483-5p causes suppression of PCa cell growth and invasion [15]. The current study aims to explore the underlying molecular mechanisms of the interplay between LINC00908, TSPYL5, and miR-483-5p in the development of PCa in a bid to discover a promising competitive new target for PCa treatment
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