a Department of Gynaecology and Obstetrics , Cangzhou Central Hospital , Cangzhou City , China.
Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):556-564. doi: 10.1080/21691401.2019.1575840.
Long noncoding RNA lung cancer associated transcript 1 (LUCAT1) has been shown to be a lncRNA that facilitates the development and progression of several tumours. However, the evidence of LUCAT1 modulating the growth and metastasis of cervical cancer (CC) were still lacking. The present study aimed to explore the expression pattern, biological function and potential mechanism of LUCAT1 in CC. In this study, we, first, confirmed that LUCAT1 acted as an up-regulated lncRNA by analyzing the data from GCTA dataset and RT-PCR in both CC tissues and cell lines. We also showed that TINCR overexpression is induced by nuclear transcription factor SP1. Then, clinical assays showed that LUCAT1 was associated with advanced clinical progression and poor prognosis of CC patients. Importantly, multivariate Cox model confirmed that LUCAT1 expression was an independent prognostic factor for both 5-year overall survival in CC. Then, lost-function assays revealed that knockdown of LUCAT1 significantly suppressed CC cells proliferation, colony formation, migration, invasion and EMT by a series of cells experiments. Mechanistically, Bioinformatic tools predicted that miR-181a may target LUCAT1, which was confirmed using luciferase reporter assay and RNA immunoprecipitation (RIP) assays. Overall, our findings showed that SP1-activated LUCAT1 exerts an oncogenic function in CC by binding to miR-181a, suggesting that miR-181a may be a ponderable and promising therapeutic target for CC.
长链非编码 RNA 肺癌相关转录本 1（LUCAT1）已被证明是一种促进多种肿瘤发生和发展的 lncRNA。然而，LUCAT1 调节宫颈癌（CC）生长和转移的证据仍然缺乏。本研究旨在探讨 LUCAT1 在 CC 中的表达模式、生物学功能和潜在机制。在这项研究中，我们首先通过分析 GCTA 数据集和 CC 组织和细胞系中的 RT-PCR 数据，证实了 LUCAT1 作为一种上调的 lncRNA 发挥作用。我们还表明，TINCR 的过表达是由核转录因子 SP1 诱导的。然后，临床检测表明 LUCAT1 与 CC 患者的晚期临床进展和不良预后相关。重要的是，多变量 Cox 模型证实 LUCAT1 表达是 CC 患者 5 年总生存率的独立预后因素。然后，失活功能检测表明，通过一系列细胞实验，敲低 LUCAT1 可显著抑制 CC 细胞的增殖、集落形成、迁移、侵袭和 EMT。机制上，生物信息学工具预测 miR-181a 可能靶向 LUCAT1，这通过荧光素酶报告基因检测和 RNA 免疫沉淀（RIP）实验得到证实。总之，我们的研究结果表明，SP1 激活的 LUCAT1 通过与 miR-181a 结合在 CC 中发挥致癌作用，提示 miR-181a 可能是 CC 一个有价值和有前途的治疗靶点。
