Long non-coding RNA lncHUPC1 induced by FOXA1 promotes tumor progression by inhibiting apoptosis via miR-133b/SDCCAG3 in prostate cancer.

Long non-coding RNAs (lncRNAs) were confirmed to be involved in regulating various malignant behaviors of tumor cells in prostate cancer (PCa). Using The Cancer Genome Atlas (TCGA) prostate adenocarcinoma datasets, several endogenous competing RNA (ceRNA) networks of lncRNA/miRNA/mRNA associated with the progression-free survival (PFS) and Gleason score (GS) were identified using bioinformatics analysis. lncRNA AC004447.2 (lncHUPC1, ENSG00000269131)/miR-133b/serologically defined colon cancer antigen-3 (SDCCAG3) was a newly identified ceRNA network that affected cell growth and apoptosis in PCa. Using q-PCR, lncHUPC1 and SDCCAG3 were found to be up-regulated in PCa cells, while miR-133b was down-regulated. The same results were found in tissue samples from 70 PCa cases. It was confirmed that the knockdown of lncHUPC1 increased the expression of miR-133b and decreased that of SDCCAG3, which further increased apoptosis and inhibited cell growth, while the miR-133b inhibitor partially reversed these effects. After transfection with miR-133b mimic after lncHUPC1-knockdown, the expression of miR-133b increased while that of SDCCAG3 reduced, and the apoptosis of the cells was more obvious and the growth of the cells was slower. Therefore, lncHUPC1 was confirmed to regulate SDCCAG3 by binding to miR-133b. Additionally, we found that the transcription factor Forkhead Box A1 (FOXA1) directly bound to the promoter of lncHUPC1 to activate it. In conclusion, the ceRNA network of lncHUPC1/miR-133b/SDCCAG3 affected the growth and apoptosis of PCa cells, and FOXA1 may be involved in the process as a transcription factor of lncHUPC1.