LncRNA FOXP4-AS1 is activated by PAX5 and promotes the growth of prostate cancer by sequestering miR-3184-5p to upregulate FOXP4

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.

Identify potential clinical significance of long noncoding RNA forkhead box P4 antisense RNA 1 in patients with early stage pancreatic ductal adenocarcinoma

“…Yang et al established that FOXP4-AS1 is significantly up-regulated in osteosarcoma tumor tissues, besides its high expression can significantly increase the danger of death and recurrence in patients with In vivo and in vitro functional experiments suggest that FOXP4-AS1 plays an oncogene role in PCa. 10 In this study, we have reported that patients with higher manifestation of FOXP4-AS1 in PDAC tumor tissues had significantly shorter OS times than patients with low FOXP4-AS1. Our results are consistent with the results of previous studies.…”

“…Survival analysis found that patients with high expression of FOXP4‐AS1 had a poor outcome. In vivo and in vitro functional experiments suggest that FOXP4‐AS1 plays an oncogene role in PCa . In this study, we have reported that patients with higher manifestation of FOXP4‐AS1 in PDAC tumor tissues had significantly shorter OS times than patients with low FOXP4‐AS1.…”

“…Previous studies have reported that lncRNA forkhead box P4 antisense RNA 1 (FOXP4‐AS1) is suggestively up‐regulated in colorectal cancer (CRC) tumor tissues; besides higher expression of FOXP4‐AS1 is correlated with poor outcome in CRC . Similar results can be observed in prostate cancer (PCa) and osteosarcoma . However, the clinical significance of FOXP4‐AS1 in various cancers remains unclear, including pancreatic cancer.…”

“…Previously, there have been few reports on its relationship in tumors. After reviewing the literature, we found that preceding studies have documented the clinical values of FOXP4‐AS1 in PCa, CRC and osteosarcoma, as well as its biological function in cancers. Previously published studies have confirmed that FOXP4‐AS1 is significantly up‐regulated in CRC tumor tissues .…”

“…8 Similar results can be observed in prostate cancer (PCa) and osteosarcoma. 9,10 However, the clinical significance of FOXP4-AS1 in various cancers remains unclear, including pancreatic cancer. The goal of this study is to identify the potential clinical significance of lncRNA FOXP4-AS1 in patients with early stage PDAC, including the prognosis value, functional mechanism, and potential small molecule drugs of target therapy.…”