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

Abstract

ObjectiveTo 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.ResultsPlncRNA-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 MethodsThe 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.ConclusionsPlncRNA-1 is an oncogene that regulates the cell cycle, cyclin-D1 and EMT in prostate cancer cells through the TGF-β1 pathway.

Retracted: Suppression of long non‐coding RNA LET potentiates bone marrow‐derived mesenchymal stem cells (BMSCs) proliferation by up‐regulating TGF‐β1

“…TGF‐β1 has been demonstrated to associate with proliferation, differentiation and apoptosis of various cell types . Zhang et al indicated that small concentrations of TGF‐β1 promoted the proliferation of BMSCs via activation of Wnt/β‐catenin pathway Several studies have presented the regulatory effects of lncRNAs on the expressions of TGF‐β1 in breast cancer and prostate cancer cells . In this research, we conducted qRT‐PCR and Western blot to analyze the association between TGF‐β1 and LET.…”

The prognostic value of long non-coding RNA PlncRNA-1 in patients with cancers: a systematic review and meta-analysis

“…LncRNAs have become a hot topic as diagnostic markers of diseases. The transcriptional level of PlncRNA-1 is signi cantly elevated in multiple malignancies, and PlncRNA-1 acts as a transcriptional regulator of various developmental processes [17][18][19][20][21][22][23][24][25]. In several human tumours, overexpression of PlncRNA-1 is related to poor OS, high TNM classi cation, advanced clinical stage, low histological differentiation, and poor vital status [20,22,24,[32][33][34].…”

“…PlncRNA-1 is ubiquitously expressed in the prostate, salivary glands and 25 other tissues. It has been shown that PlncRNA-1 plays an important role in various cancer types, including prostate cancer, colorectal cancer, osteosarcoma, glioma and oesophageal squamous carcinoma [17][18][19][20][21][22][23][24][25][26]. Accumulating evidence has demonstrated that PlncRNA-1 acts as a transcriptional regulator to modify various developmental processes.…”

“…Accumulating evidence has demonstrated that PlncRNA-1 acts as a transcriptional regulator to modify various developmental processes. For example, upregulated PlncRNA-1 expression can modulate apoptosis and proliferation and induce epithelial-mesenchymal transition [17][18][19][20][21][22][23][24][25].…”

A novel long noncoding RNA LINC00844 regulates prostate cancer cell migration and invasion through androgen receptor signaling

“…Next, we focused on understanding the underlying mechanism on how LINC00844 might control the expression of androgen-regulated genes. Previously, our lab and others have demonstrated that AR collaborative factors such as NKX3-1 [27] and lncRNAs like PlncRNA [33,34] act through a feed forward mechanism to regulate AR mRNA and protein levels to influence the expression of downstream AR target genes. Thus, we examined if LINC00844 could also function in a similar fashion.…”