Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Department of Oncology, Taizhou People's Hospital Affiliated to Nantong University, Taizhou, Jiangsu, China.
IUBMB Life. 2020 Mar;72(3):401-412. doi: 10.1002/iub.2196. Epub 2019 Nov 19.
The expression of long noncoding RNAs (lncRNAs) is closely associated with cancer development and progression, making these lncRNAs potentially novel therapeutic targets. In this study, we aimed to explore the potential function of lncRNA-uc061hsf.1 in esophageal squamous cell carcinoma (ESCC). The expression of lncRNA-uc061hsf.1 in ESCC tissues and cell lines was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation, apoptosis, and metastasis were detected via CCK-8, flow cytometry, and Transwell assays. The interaction between p53 and lncRNA uc061hsf.1 was analyzed using luciferase reporter gene and qRT-PCR. Through this approach, we identified the novel lncRNA uc061hsf.1, which was expressed in low level in ESCC and was correlated with lymph node metastasis and poor differentiation in ESCC patients. Knockdown or overexpression of lncRNA uc061hsf.1 in ESCC cells promoted or inhibited cell proliferation and metastasis, respectively. Mechanistically, lncRNA uc061hsf.1 was induced by p53, and luciferase reporter gene confirmed that lncRNA uc061hsf.1 was a direct transcriptional target of p53. We further found that uc061hsf.1 was able to regulate expression of the transcription factor FoxA1, thereby potentially influencing tumor cell migration. In conclusion, these results suggest that p53-regulated lncRNA uc061hsf.1 is a cancer suppressor gene which is associated with tumor progression in ESCC.
长链非编码 RNA(lncRNAs)的表达与癌症的发生和发展密切相关,这使得这些 lncRNAs 成为潜在的新型治疗靶点。在本研究中,我们旨在探索 lncRNA-uc061hsf.1 在食管鳞状细胞癌(ESCC)中的潜在功能。通过实时定量聚合酶链反应(qRT-PCR)检测 lncRNA-uc061hsf.1 在 ESCC 组织和细胞系中的表达。通过 CCK-8、流式细胞术和 Transwell 实验检测细胞增殖、凋亡和转移。通过荧光素酶报告基因和 qRT-PCR 分析 p53 与 lncRNA uc061hsf.1 之间的相互作用。通过这种方法,我们鉴定了新型 lncRNA uc061hsf.1,它在 ESCC 中的表达水平较低,与 ESCC 患者的淋巴结转移和低分化相关。在 ESCC 细胞中敲低或过表达 lncRNA uc061hsf.1 分别促进或抑制细胞增殖和转移。机制上,lncRNA uc061hsf.1 由 p53 诱导,荧光素酶报告基因证实 lncRNA uc061hsf.1 是 p53 的直接转录靶标。我们进一步发现 uc061hsf.1 能够调节转录因子 FoxA1 的表达,从而可能影响肿瘤细胞迁移。总之,这些结果表明,p53 调节的 lncRNA uc061hsf.1 是一种与 ESCC 肿瘤进展相关的肿瘤抑制基因。