Department of Urology, China and Japan Union Hospital of Jilin University, Changchun, 130033, P.R. China.
Exp Physiol. 2020 May;105(5):793-808. doi: 10.1113/EP088011. Epub 2020 Apr 22.
What is the central question of this study? What is the role of lncRNA PRRT3-AS1 in the regulation of peroxisome proliferator-activated receptor γ (PPARγ) gene-mediated mechanistic target of rapamycin (mTOR) signalling pathway in proliferation, apoptosis and autophagy of prostate cancer cells? What is the main finding and its importance? The targeting relation between lncRNA PRRT3-AS1 and PPARγ was verified, and it was demonstrated that silencing of lncRNA PRRT3-AS1 can upregulate apoptosis and autophagy yet downregulate proliferation, migration and invasion of prostate cancer cells through the mTOR signalling pathway. Further work is needed to consolidate the therapeutic value of lncRNA PRRT3-AS1 in clinical trials and treatment of prostate cancer.
Although long non-coding RNAs (lncRNAs) are correlated with multiple cancers, their molecular mechanisms in prostate cancer (PC) remain inadequately understood. This study investigated the effects of lncRNA PRRT3-AS1 on the progression of prostate cancer (PC) with involvement of peroxisome proliferator-activated receptor γ (PPARγ). Microarray analysis was used to identify the differentially expressed genes and lncRNAs associated with PC. RT-qPCR and western blot analysis were employed to test the expression of lncRNA PRRT3-AS1, mammalian target of rapamycin (mTOR) signalling pathway-, apoptosis- and autophagy-related genes. A scratch test, Transwell assay, CCK-8 assay, colony formation assay, flow cytometry and monodansylcadaverine staining were employed to identify the migration, invasion, proliferation activity, cell cycle and apoptosis and autophagy of PC3 cells, respectively. Tumorigenicity assays in nude mice were used to detect the tumorigenic ability. GSE55945 and GSE46602 datasets indicated that lncRNA PRRT3-AS1 was highly expressed in PC. PPARγ was predicted as a target gene of lncRNA PRRT3-AS1. Ectopic overexpression of PPARγ or lncRNA PRRT3-AS1 silencing led to inhibited cell viability, migration and invasion, and accelerated apoptosis. Furthermore, the delivery of si-PRRT3-AS1 or PPARγ vector to PC3 cells resulted in the regression of xenografts in nude mice. Based on the in vitro and in vivo experiments, silencing of lncRNA PRRT3-AS1 was observed to activate the PPARγ gene, which in turn could inhibit PC cell proliferation and promote apoptosis and autophagy by blocking the mTOR signalling pathway.
本研究的核心问题是什么？长链非编码 RNA（lncRNA）PRRT3-AS1 在调节过氧化物酶体增殖物激活受体γ（PPARγ）基因介导的雷帕霉素（mTOR）信号通路对前列腺癌细胞增殖、凋亡和自噬的机制靶点中的作用是什么？主要发现及其重要性是什么？验证了 lncRNA PRRT3-AS1 与 PPARγ 的靶向关系，结果表明沉默 lncRNA PRRT3-AS1 可通过 mTOR 信号通路上调前列腺癌细胞的凋亡和自噬，而下调其增殖、迁移和侵袭。需要进一步的工作来巩固 lncRNA PRRT3-AS1 在临床试验和前列腺癌治疗中的治疗价值。
尽管长链非编码 RNA（lncRNA）与多种癌症相关，但它们在前列腺癌（PC）中的分子机制仍了解不足。本研究探讨了 lncRNA PRRT3-AS1 对过氧化物酶体增殖物激活受体γ（PPARγ）参与的前列腺癌（PC）进展的影响。采用微阵列分析鉴定与 PC 相关的差异表达基因和 lncRNA。RT-qPCR 和 Western blot 分析检测 lncRNA PRRT3-AS1、哺乳动物雷帕霉素靶蛋白（mTOR）信号通路、凋亡和自噬相关基因的表达。划痕试验、Transwell 试验、CCK-8 试验、集落形成试验、流式细胞术和单丹磺酰尸胺染色分别用于鉴定 PC3 细胞的迁移、侵袭、增殖活性、细胞周期和凋亡和自噬。裸鼠肿瘤生成实验用于检测致瘤能力。GSE55945 和 GSE46602 数据集表明 lncRNA PRRT3-AS1 在 PC 中高表达。预测 PPARγ 是 lncRNA PRRT3-AS1 的靶基因。过表达 PPARγ 或沉默 lncRNA PRRT3-AS1 可抑制细胞活力、迁移和侵袭，并加速凋亡。此外，向 PC3 细胞递送 si-PRRT3-AS1 或 PPARγ 载体可导致裸鼠异种移植物消退。基于体外和体内实验，沉默 lncRNA PRRT3-AS1 可激活 PPARγ 基因，进而通过阻断 mTOR 信号通路抑制 PC 细胞增殖并促进凋亡和自噬。
