长链非编码RNA ASB16-AS1通过调控miR-1827/FZD4轴及激活Wnt/β-连环蛋白通路促进肝癌的生长和侵袭。
LncRNA ASB16-AS1 Promotes Growth And Invasion Of Hepatocellular Carcinoma Through Regulating miR-1827/FZD4 Axis And Activating Wnt/β-Catenin Pathway.
作者信息
Yao Xiaoxiao, You Guangqiang, Zhou Chen, Zhang Dan
机构信息
Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital of Jilin University, Changchun 130041, People's Republic of China.
Personnel Department, The First Affiliated Hospital of Jilin University, Changchun 130000, People's Republic of China.
出版信息
Cancer Manag Res. 2019 Nov 7;11:9371-9378. doi: 10.2147/CMAR.S220434. eCollection 2019.
BACKGROUND
To date, although several long noncoding RNAs (lncRNAs) are reported to regulate hepatocellular carcinoma (HCC) development, their relationship still remains elusive. ASB16-AS1 is a poorly researched novel lncRNA. We aimed to investigate its function in HCC progression.
METHODS
qRT-PCR and in situ hybridization (ISH) were used to analyze ASB16-AS1 expression in HCC tissues. CCK8, Edu incorporation and colony formation were used to determine cell proliferation. Transwell assay was used to examine migration and invasion. Luciferase reporter assay was used to analyze the interactions among ASB16-AS1, miR-1827 and FZD4.
RESULTS
Bioinformatics analysis identified ASB16-AS1 was overexpressed in HCC tissues, which was further validated by qRT-PCR and in situ hybridization (ISH). Besides, ASB16-AS1 was demonstrated to be a potential indicator for HCC prognosis. Functional studies showed ASB16-AS1 knockdown attenuated proliferation, migration and invasion of HCC cells. Mechanistically, ASB16-AS1 directly interacted with miR-1827 and promoted FZD4 expression by sponging miR-1827. Overexpressed FZD4 eventually activated Wnt/β-catenin pathway and contributed to HCC progression.
CONCLUSION
Our work is the first to identify ASB16-AS1 as an oncogene that enhances HCC progression by modulating miR-1827/FZD4/Wnt/β-catenin pathways.
背景
迄今为止，尽管有报道称几种长链非编码RNA（lncRNA）可调节肝细胞癌（HCC）的发展，但其关系仍不清楚。ASB16-AS1是一种研究较少的新型lncRNA。我们旨在研究其在HCC进展中的作用。
方法
采用qRT-PCR和原位杂交（ISH）分析ASB16-AS1在HCC组织中的表达。采用CCK8、Edu掺入法和集落形成法测定细胞增殖。采用Transwell实验检测迁移和侵袭能力。采用荧光素酶报告基因实验分析ASB16-AS1、miR-1827和FZD4之间的相互作用。
结果
生物信息学分析显示ASB16-AS1在HCC组织中高表达，qRT-PCR和原位杂交（ISH）进一步验证了这一结果。此外，ASB16-AS1被证明是HCC预后的一个潜在指标。功能研究表明，敲低ASB16-AS1可减弱HCC细胞的增殖、迁移和侵袭能力。机制上，ASB16-AS1直接与miR-1827相互作用，通过海绵吸附miR-1827促进FZD4表达。FZD4过表达最终激活Wnt/β-连环蛋白通路，促进HCC进展。
结论
我们的研究首次确定ASB16-AS1是一种癌基因，它通过调节miR-1827/FZD4/Wnt/β-连环蛋白通路促进HCC进展。
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