Abstract
Prostate cancer (PCa) is one of the major men malignancies worldwide. Long noncoding RNAs (lncRNAs) have been reported as essential regulators in human cancers, including PCa. In the present study, lncRNA forkhead box P4 antisense RNA 1 (FOXP4-AS1) was found to be highly expressed in TCGA PCa samples. Upregulation of FOXP4-AS1 was further validated in 64 PCa tissues and predicted poor prognosis in patients with PCa. Functionally, high FOXP4-AS1 level was associated with increased cell proliferation and decreased cell apoptosis, indicating that FOXP4-AS1 exerted oncogenic functions in the tumorigenesis of PCa. Furthermore, FOXP4-AS1 was located in the cytoplasm of PCa cell lines and positively regulated FOXP4. LncRNAs can exert their functions by cooperating with their nearby genes. Mechanistically, FOXP4-AS1 post-transcriptionally regulated FOXP4 by acting as a competing endogenous RNA (ceRNA) in PCa to sponge miR-3184-5p. Considering the upregulation of both FOXP4-AS1 and its nearby gene FOXP4, we further detected the coactivator of FOXP4-AS1 and FOXP4. Mechanism analysis indicated that paired box 5 (PAX5) transcriptionally activated FOXP4-AS1 and FOXP4 in PCa. Collectively, we determined that PAX5-induced upregulation of FOXP4-AS1/FOXP4 axis promoted tumorigenesis of PCa.
Highlights
Prostate cancer (PCa) is a commonly diagnosed malignant male cancer and is one of the prime reasons for cancer-related death[1]
Recently, increasing number of researches has revealed the crucial role of long noncoding RNAs (lncRNAs) in tumorigenesis[20,21,22]
Dysregulation of lncRNAs is closely correlated with the overall survival of patients with cancer
Summary
Prostate cancer (PCa) is a commonly diagnosed malignant male cancer and is one of the prime reasons for cancer-related death[1]. Lacking of the biomarker in early diagnosis resulted in low overall survival of patients with PCa. numerous efforts have been made in exploring the novel therapeutic strategies, the prognosis of patients with advanced PCa remains unfavorable. Exploring the molecular mechanism associated with the tumorigenesis of PCa is of great significance for the early diagnosis or treatment of PCa. Recent years, long noncoding RNAs (lncRNAs) that are mainly transcribed from the genomic intergenic regions have become a research focus in cancers transcriptome[2]. Long noncoding RNAs (lncRNAs) that are mainly transcribed from the genomic intergenic regions have become a research focus in cancers transcriptome[2] They have been demonstrated to be participants in various biological processes by different mechanisms[3,4]. Some lncRNAs have been defined to be PCa specific, such as PCGEM18, PRNCR19, PCAT110, and SChLAP111
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