长链非编码 RNA TUG1 通过 Nrf2 信号轴调节前列腺癌细胞的增殖、侵袭和迁移。
Long noncoding RNA TUG1 regulates prostate cancer cell proliferation, invasion and migration via the Nrf2 signaling axis.
机构信息
Department of Urology Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, PR China; Central Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, PR China.
Department of Urology Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, PR China; Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, PR China.
出版信息
Pathol Res Pract. 2020 Apr;216(4):152851. doi: 10.1016/j.prp.2020.152851. Epub 2020 Feb 5.
BACKGROUND
Long noncoding RNAs (lncRNAs) have been identified to modulate the development and progression of prostate cancer (PCa) via the regulation of their target genes. However, the biological function underlying the effect of lncRNA TUG1 in PCa remains unclear.
METHODS
Reverse transcription-quantitative polymerase chain reaction (qRT-PCR) and Western blotting analysis were used to assess the mRNA expression of TUG1 and protein expression levels of Nrf2 pathway members, respectively. The migration, invasion, and proliferation abilities of cells were assessed by the wound-healing, Transwell migration/invasion, and CCK8 assays, respectively.
RESULTS
TUG1 was strikingly upregulated in PCa cells compared with non-tumorigenic human prostate epithelial cells. The LncTar Web Server, which is a bioinformatics tool, was used to predict the target association between TUG1 and Nrf2. Moreover, the expression of TUG1 showed a strikingly positive correlation with that of Nrf2 in TCGA PCa RNA-Seq data (r = 0.26,P = 4.63E-09). Subsequently, inhibition of TUG1 using siRNA resulted in deceased proliferation, migration, and invasion of PCa cells; however, these effects were reversed by treatment with oltipraz (an activator of Nrf2). Finally, we evaluated the Nrf2 pathway to reveal the underlying mechanism of TUG1 in PCa cells, and found that TUG1 knockdown decreased the protein expression of Nrf2 downstream members (e.g., HO-1, FTH1, and NQO1).
CONCLUSIONS
LncRNA TUG1 plays an oncogenic role in human PCa cells by promoting the cell proliferation and invasion in PCa cell lines, at least partly via the Nrf2 signaling pathway.
背景
长链非编码 RNA（lncRNA）已被鉴定通过调节其靶基因来调节前列腺癌（PCa）的发展和进展。然而，lncRNA TUG1 在 PCa 中的作用的生物学功能仍不清楚。
方法
使用逆转录定量聚合酶链反应（qRT-PCR）和 Western blot 分析分别评估 TUG1 的 mRNA 表达和 Nrf2 通路成员的蛋白表达水平。通过划痕愈合、Transwell 迁移/侵袭和 CCK8 测定分别评估细胞的迁移、侵袭和增殖能力。
结果
与非肿瘤性人前列腺上皮细胞相比，PCa 细胞中 TUG1 的表达明显上调。LncTar Web 服务器是一种生物信息学工具，用于预测 TUG1 和 Nrf2 之间的靶关联。此外，TCGA PCa RNA-Seq 数据中的 TUG1 表达与 Nrf2 的表达呈显著正相关（r=0.26，P=4.63E-09）。随后，使用 siRNA 抑制 TUG1 导致 PCa 细胞的增殖、迁移和侵袭减少；然而，这些效应被 oltipraz（Nrf2 的激活剂）处理所逆转。最后，我们评估了 Nrf2 通路，以揭示 TUG1 在 PCa 细胞中的潜在机制，发现 TUG1 敲低降低了 Nrf2 下游成员（如 HO-1、FTH1 和 NQO1）的蛋白表达。
结论
lncRNA TUG1 通过促进 PCa 细胞系中的细胞增殖和侵袭，在人 PCa 细胞中发挥致癌作用，至少部分通过 Nrf2 信号通路。
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