Upregulation of long non-coding RNA PlncRNA-1 promotes proliferation and induces epithelial-mesenchymal transition in prostate cancer

// Yang Jin 1, 3 , Zilian Cui 2, 3 , Xudong Li 4 , Xunbo Jin 3 , Jian Peng 1 1 Department of Hepatobiliary Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China 2 Shandong University School of Medicine, Jinan, Shandong, China 3 Minimally Invasive Urology Center, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong, China 4 Department of Urology, Binzhou People's Hospital, Binzhou, Shandong, China Correspondence to: Zilian Cui, email: 122526195@qq.com Keywords: PlncRNA-1, long noncoding RNA, LNCAP, C4-2, TGF-β1 Received: October 19, 2016 Accepted: January 29, 2017 Published: February 13, 2017 ABSTRACT Objective: To confirm that PlncRNA-1 regulates the cell cycle in prostate cancer cells and induces epithelial-mesenchymal transition (EMT) in prostate cancer through the TGF-β1 pathway. Results: PlncRNA-1 and TGF-β1 expression levels were significantly higher in prostate cancer tissues than in normal prostate tissues ( P < 0.05) and were significantly positively correlated. TGF-β1, N-cadherin and Cyclin-D1 were downregulated and E-Cadherin was upregulated in LNCAP cells after silencing of PlncRNA-1, as determined by real-time PCR and Western blot. TGF-β1, N-cadherin and Cyclin-D1 were upregulated and E-cadherin was downregulated in C4-2 cells, as determined by real-time PCR and Western blot. Overexpression of PlncRNA-1 in C4-2 cells was observed when TGF-β1 inhibitor LY2109761 was added. Western blot analysis showed that compared with their expression when TGF-β1 inhibitor LY2109761 was not added, N-Cadherin and CyclinD1 expression decreased and E-Cadherin expression increased. Transwell results showed that the invasive ability of C4-2 cells was enhanced after overexpression of PlncRNA-1, and the invasion ability was decreased after addition of TGF-β1 inhibitor LY2109761. The cell cycle was blocked by overexpression of PlncRNA-1 in C4-2 and by the addition of TGF-β1 inhibitor LY2109761, as determined by flow cytometry. In vitro experiments showed that PlncRNA-1 can regulate the growth of prostate cancer cells and EMT through the TGF-β1 pathway. In vivo experiments also confirmed the above results. Tumor growth was significantly blocked by overexpressing PlncRNA-1 in C4-2 cells and by the TGF-β1 inhibitor LY2109761 in animal experiments. Materials and Methods: The expression levels of PlncRNA-1 and TGF-β1 were analyzed in 19 prostate cancer tissue samples and in adjacent normal tissue samples, 4 Pca cell lines, including LNCaP, C4-2,DU145, and PC3, and 1 normal prostate epithelial cell line RWPE-1. LNCAP cells were divided into the LNCAP control group and the LNCAP-PlncRNA-1-siRNA group. Cells from the prostate cancer cell line C4-2 were divided into the C4-2 control group and the C4-2-PlncRNA-1 experimental group. Changes in TGF-β1, E-cadherin and N-cadherin were detected by qPCR and Western Blot assay after silencing and overexpression of PlncRNA-1. The cell cycle, cell invasion, and levels of Cyclin-D1, E-Cadherin, and N-Cadherin were observed after adding TGF-β1 inhibitor LY2109761 in the C4-2-PlncRNA-1 group. The effects of TGF-β1 inhibitor LY2109761 on the tumorigenicity of C4-2 cells after overexpression of PlncRNA-1 was investigated in vivo . Conclusions: PlncRNA-1 is an oncogene that regulates the cell cycle, cyclin-D1 and EMT in prostate cancer cells through the TGF-β1 pathway.