Abstract
BackgroundLong noncoding RNAs (lncRNAs) are important functional regulators of many biological processes of cancers. However, the mechanisms by which lncRNAs modulate androgen-independent prostate cancer (AIPC) development remain largely unknown.MethodsNext-generation sequencing technology and RT-qPCR were used to assess LEF1-AS1 expression level in AIPC tissues and adjacent normal tissues. Functional in vitro experiments, including colony formation, EDU and transwell assays were performed to assess the role of LEF1-AS1 in AIPC. Xenograft assays were conducted to assess the effect of LEF1-AS1 on cell proliferation in vivo. Chromatin immunoprecipitation (ChIP) and RNA binding protein immunoprecipitation (RIP) assays were performed to elucidate the regulatory network of LEF1-AS1.ResultsThe next-generation sequencing results showed that LEF1-AS1 is significantly overexpressed in AIPC. Furthermore, our RT-qPCR assay data showed that LEF1-AS1 is overexpressed in AIPC tissues. Functional experiments showed that LEF1-AS1 promotes the proliferation, migration, invasion and angiogenic ability of AIPC cells in vitro and tumour growth in vivo by recruiting the transcription factor C-myb to the promoter of FZD2, inducing its transcription. Furthermore, LEF1-AS1 was shown to function as a competing endogenous RNA (ceRNA) that sponges miR-328 to activate CD44.ConclusionIn summary, the results of our present study revealed that LEF1-AS1 acts as a tumour promoter in the progression of AIPC. Furthermore, the results revealed that LEF1-AS1 functions as a ceRNA and regulates Wnt/β-catenin pathway activity via FZD2 and CD44. Our results provide new insights into the mechanism that links the function of LEF1-AS1 with AIPC and suggests that LEF1-AS1 may serve as a novel potential target for the improvement of AIPC therapy.
Highlights
IntroductionLong noncoding RNAs (lncRNAs) are important functional regulators of many biological processes of cancers
Long noncoding RNAs are important functional regulators of many biological processes of cancers
We identified 21 abnormally expressed Long noncoding RNAs (lncRNAs) in androgen-independent prostate cancer (AIPC) and observed that LEF1-AS1 was significantly increased in AIPC tissues (Fig. 1a) (Additional file 2: Table S2)
Summary
Long noncoding RNAs (lncRNAs) are important functional regulators of many biological processes of cancers. Long noncoding RNAs (lncRNAs) are a type of ncRNA (non-coding RNA) that lack protein-coding capacity and play a crucial role in regulating cell proliferation, apoptosis, migration, and invasion in addition to other cellular. Chakravartyet observed significantly higher lncRNA NEAT1 in tumour tissues than in adjacent tissues during AIPC progression, which significantly increased cell proliferation by regulating the epigenetic signatures of target gene promoters [7]. Several studies have demonstrated that LEF1-AS1 promotes cell proliferation and invasion during multiple types of cancers in recent years, suggesting that LEF1-AS1 can function as an oncogene and may be a potential therapeutic target to inhibit the progress of malignancy [10, 11]. Increasing experimental evidence suggests that lncRNAs can sponge miRNAs and interact with proteins to regulate the expression of tumour-related genes and signalling pathways
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