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高表达的长链非编码RNA NNT-AS1通过Wnt/β-连环蛋白信号通路促进宫颈癌细胞的增殖和侵袭。

Highly expressed long non-coding RNA NNT-AS1 promotes cell proliferation and invasion through Wnt/β-catenin signaling pathway in cervical cancer.

作者信息

Hua Fangfang, Liu Shanshan, Zhu Lihong, Ma Ning, Jiang Shan, Yang Jun

机构信息

Department of Gynecology, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, PR China.

Department of Gynecology and Obstetrics, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, PR China.

出版信息

Biomed Pharmacother. 2017 Aug;92:1128-1134. doi: 10.1016/j.biopha.2017.03.057. Epub 2017 Jun 13.

Abstract

BACKGROUND

Cervical cancer is the most common gynecological malignancies in women worldwide. The previous study showed that lncRNA NNT-AS1 could play an important role in tumor development and metastasis of colorectal cancer. However, little is known about the function of NNT-AS1 in cervical cancer. The aim of this study was to investigate the expression profile of NNT-AS1 in cervical cancer and assess its possible molecular mechanism.

METHODS

Relative expression levels of NNT-AS1 in cervical cancer tissues were determined by qRT-PCR. The biologic functions of NNT-AS1 in cervical cancer were explored by MTT assay, transwell assay and flow cytometric analysis in vitro. The influence of NNT-AS1 on tumorigenesis was measured by mice xenograft model. In addition, we evaluated the activation of Wnt/β-catenin signaling pathway by luciferase assay and western blot.

RESULTS

Our results showed that NNT-AS1 expression in cervical cancer tissues compared with adjacent non-tumor tissues the overexpression of NNT-AS1 was positively associated with advanced FIGO stage, lymph node metastasis, depth of cervical invasion and poorer overall survival. Function assays showed that NNT-AS1 inhibition could suppress cervical cancer cells proliferation and invasion ability in vitro as well as the activation of Wnt/β-catenin signaling pathway. In vivo mice xenograft model revealed that silencing NNT-AS1 could reduce tumor growth in nude mice.

CONCLUSIONS

The results of the current study suggested that NNT-AS1 might play an important role in cervical carcinogenesis and might serve as a potentially therapeutic target and prognostic marker in the treatment of cervical cancer.

摘要

背景

宫颈癌是全球女性中最常见的妇科恶性肿瘤。先前的研究表明,lncRNA NNT-AS1在结直肠癌的肿瘤发生和转移中可能发挥重要作用。然而,关于NNT-AS1在宫颈癌中的功能知之甚少。本研究的目的是调查NNT-AS1在宫颈癌中的表达谱,并评估其可能的分子机制。

方法

通过qRT-PCR测定宫颈癌组织中NNT-AS1的相对表达水平。体外通过MTT法、Transwell法和流式细胞术分析探讨NNT-AS1在宫颈癌中的生物学功能。通过小鼠异种移植模型检测NNT-AS1对肿瘤发生的影响。此外,我们通过荧光素酶报告基因检测和蛋白质免疫印迹评估Wnt/β-连环蛋白信号通路的激活情况。

结果

我们的结果显示,与相邻非肿瘤组织相比,宫颈癌组织中NNT-AS1的表达,NNT-AS1的过表达与国际妇产科联盟(FIGO)晚期、淋巴结转移、宫颈浸润深度和较差的总生存率呈正相关。功能试验表明,抑制NNT-AS1可在体外抑制宫颈癌细胞的增殖和侵袭能力以及Wnt/β-连环蛋白信号通路的激活。体内小鼠异种移植模型显示,沉默NNT-AS1可减少裸鼠体内肿瘤的生长。

结论

本研究结果表明,NNT-AS1可能在宫颈癌发生中起重要作用,并可能作为宫颈癌治疗中潜在的治疗靶点和预后标志物。

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