OBJECTIVE: The aim of this study was to investigate the specific role of Taurine up-regulated gene 1 (TUG1) in the development of prostate cancer (PCa), and to explore its underlying mechanism.
PATIENTS AND METHODS: The serum level of TUG1 in healthy subjects, benign prostatic hyperplasia (BPH) patients and PCa patients was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The correlation between TUG1 expression and clinical indexes of PCa patients was analyzed. TUG1 expression in PCa cells and human normal prostate cells was determined by qRT-PCR as well. Overexpression or knockdown of TUG1 was achieved by liposomal transfection. Subsequently, the regulatory effects of TUG1 on the proliferative and migratory capacities of DU145 cells were accessed by Cell Counting Kit-8 (CCK-8) assay, colony formation assay and transwell assay, respectively. An online software was used to predict whether RLIM could be regulated by TUG1, which was further verified by qRT-PCR. After RLIM knockdown in DU145 cells, the proliferative and migratory capacities were also determined. Finally, Western blot was conducted to determine relative protein expressions in the TGF-β1/Smad pathway after altering TUG1 expression in DU145 cells.
RESULTS: TUG1 was highly expressed in serum samples of PCa patients when compared with healthy subjects and BPH patients. Besides, TUG1 expression in PCa patients with Gleason ≥ 7 was significantly higher than those with Gleason < 7. Meanwhile, TUG1 expression in PCa patients was remarkably higher than that of BPH patients at the PSA grey zone (4-10 ng/mg). ROC curves indicated that TUG1 might be a crucial hallmark to distinguish PCa patients from BPH patients and healthy subjects. The overexpression of TUG1 markedly promoted the proliferative and migratory capacities of DU145 cells. However, knockdown of TUG1 obtained the opposite results. QRT-PCR confirmed that TUG1 was positively correlated with RLIM at the mRNA level. RLIM knockdown significantly inhibited the proliferative and migratory capacities of DU145 cells. Furthermore, knockdown of TUG1 in DU145 cells markedly down-regulated TGF-β1 and p-Smad2, whereas up-regulated p-Smad7.
CONCLUSIONS: TUG1 is highly expressed in peripheral blood of PCa patients, which can serve as a potential diagnostic marker for PCa. The overexpression of TUG1 promotes the proliferative and migratory capacities of PCa cells. Furthermore, TUG1 promotes the development of PCa by regulating RLIM through the TGF-β1/Smad pathway.Free PDF Download
To cite this article
B.-H. Guo, Q. Zhao, H.-Y. Li
TUG1 promotes the development of prostate cancer by regulating RLIM
Eur Rev Med Pharmacol Sci
Vol. 23 - N. 5