长链非编码RNA NCK1-AS1通过miR-22-3p/YARS轴激活PI3K/AKT信号通路加重肝细胞癌

LncRNA NCK1-AS1 Aggravates Hepatocellular Carcinoma by the miR-22-3p/YARS Axis to Activate PI3K/AKT Signaling.

作者信息

Zhou Weixin, Wang Jie, Zhang Jie, Wang Yuhan, Jiang Ling, Guo Tianhong, Luo Binrui, Xu Qi, Huang Yuanshuai

机构信息

Department of Transfusion, the Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan, China. .

Department of Transfusion, the Affiliated Hospital of Southwest Medical University, Luzhou 646000, Sichuan, China.

出版信息

J Gastrointestin Liver Dis. 2022 Mar 19;31(1):48-59. doi: 10.15403/jgld-4077.

DOI:10.15403/jgld-4077

PMID:35306563

Abstract

BACKGROUND

Hepatocellular carcinoma (HCC) is frequently diagnosed at late stages when curative treatments are no more appliable. Many studies have proved the active role of long non-coding RNAs (lncRNAs) in cancers' biology; here, the functional role of lncRNA NCK1-AS1 in HCC was identified.

METHODS

Gene expression in tumor tissues of HCC was evaluated by examining online databases and 88 collected HCC samples from our hospital. The interactions of miR-22-3p with NCK1-AS1 and tyrosyl-tRNA synthetase (YARS) were tested by conducting bioinformatics analysis, luciferase report, and RNA pulldown experiments. CCK-8, colony formation, flow cytometry, wound healing, transwell experiments were used to dissect the role of the NCK1-AS1/miR-22-3p/YARS axis in HCC.

RESULTS

NCK1-AS1 was overexpressed in HCC cells and tissues. Functional assays depicted that depletion of NCK1-AS1 hampered malignant character of HCC cells. NCK1-AS1 controlled the availability of miR-22-3p, resulting in YARS upregulation. YARS was found to have a clinical value for HCC diagnosis. Moreover, rescue experiments revealed that miR-22-3p inhibition or YARS overexpression partially blocked the function of NCK1-AS1 deficiency in HCC cells. As for the downstream signaling pathway, we discovered that NCK1-AS1 activated PI3K/AKT signaling by the miR-22-3p/YARS axis.

CONCLUSION

The present study verified that NCK1-AS1 could promote HCC progression via the miR-22-3p/YARS axis to activate PI3K/AKT signaling.

摘要

背景

肝细胞癌（HCC）在晚期常被诊断出来，此时治愈性治疗已不再适用。许多研究已证明长链非编码RNA（lncRNA）在癌症生物学中发挥着积极作用；在此，我们确定了lncRNA NCK1-AS1在HCC中的功能作用。

方法

通过在线数据库和从我院收集的88例HCC样本，评估HCC肿瘤组织中的基因表达。通过生物信息学分析、荧光素酶报告实验和RNA下拉实验，检测miR-22-3p与NCK1-AS1和酪氨酰-tRNA合成酶（YARS）之间的相互作用。采用CCK-8、集落形成、流式细胞术、伤口愈合、Transwell实验，剖析NCK1-AS1/miR-22-3p/YARS轴在HCC中的作用。

结果

NCK1-AS1在HCC细胞和组织中高表达。功能实验表明，NCK1-AS1的缺失阻碍了HCC细胞的恶性特征。NCK1-AS1控制miR-22-3p的可利用性，导致YARS上调。发现YARS对HCC诊断具有临床价值。此外，挽救实验表明，miR-22-3p抑制或YARS过表达部分阻断了NCK1-AS1缺陷在HCC细胞中的功能。至于下游信号通路，我们发现NCK1-AS1通过miR-22-3p/YARS轴激活PI3K/AKT信号通路。