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Rapidly accumulated evidence has shown that long non-coding RNA (lncRNAs) disregulation is involved in human tumorigenesis in many cancers, including prostate cancer (PCa). LncRNAs can regulate essential pathways that contribute to tumor initiation and progression with tissue specificity, which suggests that lncRNAs could be valuable biomarkers and therapeutic targets. Prostate cancer antigen 3 (PCA3), also known as differential display code 3 (DD3), is one such lncRNA that maps to chromosome 9q21-22. PCA3 expression is highly specific to PCa. In the present study, the level of PCA3 expression in prostate cancer cells was reduced by small interfering RNA (siRNA). Subsequently, the ability of LNCaP cell proliferation, invasion, and migration of PCa was compromised both in vivo and in vitro with the occurrence of cell autophagy. Recently, a novel regulatory mechanism has been proposed in which RNAs cross talk via competing with the shared microRNAs (miRNAs). In addition, lncRNAs can directly interact with RNA-binding proteins and then bind to the gene promoter region to further regulate gene expression. The proposed competitive endogenous RNAs mediate the bioavailability of miRNAs on their targets, thus imposing another level of post-transcriptional regulation. Here, we demonstrated that binding of Snail to the promoter region of PCA3 could activate the expression of PCA3. Down-regulation of PCA3 by silencing could increase the expression of the miRNA-1261, which then targeted at the PRKD3 gene (protein kinase D3) through competitive sponging. In summary, these results suggest that the transcription factor, Snail, activated the expression of lncRNA PCA3, which could inhibit the translation of PRKD3 protein via competitive miR-1261 sponging, and thus high expression of PRKD3 further promoted invasion and migration of prostate cancer.

Prostate cancer gene expression marker 1 (PCGEM1) is a long non-coding RNA (lncRNA) overexpressed in prostate cancer (PCa) cells that promotes PCa initiation and progression, and protects against chemotherapy-induced apoptosis. The microRNA miR-145 functions as a tumor suppressor in PCa. We speculate that reciprocal regulation of PCGEM1 and miR-145 promote proliferation of LNCaP prostate cancer cells. To test this hypothesis, the interaction between PCGEM1 and miR-145 was examined using a luciferase reporter assay. Expression levels were selectively altered in LNCaP cells and noncancerous RWPE-1 prostate cells by transfection of miR-145 or small interfering RNA sequences against (siRNA) PCGEM1. Relative expression levels were detected by RT-PCR, tumor cell growth and early apoptosis by the MTT assay and flow cytometry, respectively, and tumor cell migration and invasion properties by transwell assays. The effect of siRNA PCGEM1 and miR-145 transfection on prostate cancer growth in vivo was examined in the (nu/nu) mouse model. PCGEM1 and miR-145 exhibited reciprocal regulation; downregulation of PCGEM1 expression in LNCaP cells increased expression of miR-145, while overexpression of miR-145 decreased PCGEM1 expression. Transfection of the miR-145 expression vector and siRNA PCGEM1 inhibited tumor cell proliferation, migration, and invasion, and induced early apoptosis both in vitro. In contrast, there was no effect on RWPE-1 cells. We demonstrate a reciprocal negative control relationship between PCGEM1 and miR-145 that regulates both LNCaP cell proliferation and nu/nu PCa tumor growth. The results also identify PCGEM1 and associated regulators as possible targets for PCa therapy.