Department of Urology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250021, China.
Department of Human Resources, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, 250021, China.
Cell Death Dis. 2020 Dec 7;11(12):1038. doi: 10.1038/s41419-020-03240-z.
Apart from being potential prognostic biomarkers and therapeutic targets, long non-coding RNAs (lncRNAs) modulate the development and progression of multiple cancers. PlncRNA-1 is a newly discovered lncRNA that exhibits the above properties through multiple regulatory pathways. However, the clinical significance and molecular mechanisms of PlncRNA-1 in bladder cancer have not been established. PlncRNA-1 was found to be overexpressed in 71.43% of bladder cancer tissues. Moreover, the expression level correlated with tumor invasion, T stage, age, and number of tumors, but not with gender, recurrent status, preoperative treatment, pathological grade, and tumor size. The expression level of PlncRNA-1 can, to a certain extent, be used as a predictor of the degree of tumor invasion and T stage among BC patients. Inhibiting PlncRNA-1 expression impaired the proliferation, migration, and invasion of T24 and 5637 bladder cancer cells in vitro and in vivo. Specifically, PlncRNA-1 promoter in BC tissues was found to be hypomethylated at position 131 (36157603 on chromosome 21). PlncRNA-1 promoter hypomethylation induces the overexpression of PlncRNA-1. In addition, PlncRNA-1 modulated the expression of smad3 and has-miR-136-5p (miR-136). Conversely, miR-136 regulated the expression of PlncRNA-1 and smad3. PlncRNA-1 mimics competitive endogenous RNA (ceRNA) in its regulation of smad3 expression by binding miR-136. Rescue analysis further revealed that modulation of miR-136 could reverse the expression of smad3 and epithelial-mesenchymal transition (EMT) marker proteins impaired by PlncRNA-1. In summary, PlncRNA-1 has important clinical predictive values and is involved in the post-transcriptional regulation of smad3. The PlncRNA-1/miR-136/smad3 axis provides insights into the regulatory mechanism of BC, thus may serve as a potential therapeutic target and prognostic biomarker for cancer.
除了作为潜在的预后生物标志物和治疗靶点外，长链非编码 RNA（lncRNA）还调节多种癌症的发生和发展。PlncRNA-1 是一种新发现的 lncRNA，通过多种调节途径表现出上述特性。然而，PlncRNA-1 在膀胱癌中的临床意义和分子机制尚未建立。研究发现，PlncRNA-1 在 71.43%的膀胱癌组织中过度表达。此外，表达水平与肿瘤侵袭、T 分期、年龄和肿瘤数量相关，但与性别、复发状态、术前治疗、病理分级和肿瘤大小无关。PlncRNA-1 的表达水平在一定程度上可以作为 BC 患者肿瘤侵袭程度和 T 分期的预测因子。抑制 PlncRNA-1 的表达可损害 T24 和 5637 膀胱癌细胞在体外和体内的增殖、迁移和侵袭。具体来说，在 BC 组织中发现 PlncRNA-1 启动子在位置 131（21 号染色体上的 36157603）处低甲基化。PlncRNA-1 启动子低甲基化诱导 PlncRNA-1 的过表达。此外，PlncRNA-1 调节 smad3 和 has-miR-136-5p（miR-136）的表达。相反，miR-136 调节 PlncRNA-1 和 smad3 的表达。PlncRNA-1 通过与 miR-136 结合作为 ceRNA 调节 smad3 的表达。挽救分析进一步表明，miR-136 的调节可以逆转 PlncRNA-1 受损的 smad3 表达和上皮-间充质转化（EMT）标记蛋白的表达。总之，PlncRNA-1 具有重要的临床预测价值，并参与 smad3 的转录后调节。PlncRNA-1/miR-136/smad3 轴为膀胱癌的调控机制提供了新的见解，因此可能成为癌症的潜在治疗靶点和预后生物标志物。
