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.
Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. 2016 Oct 14 [Epub ahead of print]
Jin-Hua He, Bao-Xia Li, Ze-Ping Han, Mao-Xian Zou, Li Wang, Yu-Bing Lv, Jia-Bin Zhou, Ming-Rong Cao, Yu-Guang Li, Jing-Zhi Zhang
Department of Laboratory, Central Hospital of Panyu District, 8 Fuyu Dong Road, Shiqiao, Guangzhou, Guangdong, 511400, People's Republic of China., State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, China., Department of General Surgery, First Affiliated Hospital, Jinan University, Guangzhou, Guangdong, 510630, China., Department of Laboratory, Central Hospital of Panyu District, 8 Fuyu Dong Road, Shiqiao, Guangzhou, Guangdong, 511400, People's Republic of China. ., The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510620, People's Republic of China. .