He Dingdong, Zhang Xiaokang, Zhu Xinyu, Maharjan Narayani, Wang Yingchao, Luo Ping, Liang Chunzi, Tu Jiancheng
Department & Program of Clinical Laboratory Medicine, Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Wuhan, China.
Front Oncol. 2020 Dec 3;10:609601. doi: 10.3389/fonc.2020.609601. eCollection 2020.
Hepatocellular carcinoma (HCC) is one of the most common neoplastic diseases worldwide. Available biomarkers are not sensitive enough for the diagnosis of HCC, hence seeking new biomarkers of HCC is urgent and challenging. The purpose of this study was to investigate the role of F-box and leucine-rich repeat protein 19-antisense RNA 1 (FBXL19-AS1) through a functional network and inquire into its diagnostic and prognostic value in HCC. A comprehensive strategy of genomic data mining, bioinformatics and experimental validation was used to evaluate the clinical value of FBXL19-AS1 in the diagnosis and prognosis of HCC and to identify the pathways in which FBXL19-AS1 might be involved. FBXL19-AS1 was up-regulated in HCC tissues, and its high expression was associated with TNM stage and poor prognosis of HCC patients. The combination of FBXL19-AS1 and alpha-fetoprotein (AFP) in plasma could prominently improve the diagnostic validity for HCC. FBXL19-AS1 might stabilize FBXL19 to reduce the amount of macrophage M1, and then promote the occurrence and development of HCC. Meanwhile, FBXL19-AS1 might participate in regulating HCC related pathways through FBXL19-AS1-miRNA-mRNA network. Our findings indicated that FBXL19-AS1 not only serves as a potential biomarker for HCC diagnosis and prognosis, but also might be functionally carcinogenic.
肝细胞癌(HCC)是全球最常见的肿瘤性疾病之一。现有的生物标志物对HCC诊断的敏感性不足,因此寻找新的HCC生物标志物既紧迫又具有挑战性。本研究旨在通过功能网络研究F-box和富含亮氨酸重复蛋白19反义RNA 1(FBXL19-AS1)的作用,并探讨其在HCC中的诊断和预后价值。采用基因组数据挖掘、生物信息学和实验验证的综合策略,评估FBXL19-AS1在HCC诊断和预后中的临床价值,并确定FBXL19-AS1可能参与的途径。FBXL19-AS1在HCC组织中上调,其高表达与HCC患者的TNM分期和不良预后相关。血浆中FBXL19-AS1与甲胎蛋白(AFP)联合可显著提高HCC的诊断效能。FBXL19-AS1可能通过稳定FBXL19以减少M1巨噬细胞数量,进而促进HCC的发生发展。同时,FBXL19-AS1可能通过FBXL19-AS1-微小RNA-信使核糖核酸网络参与调控HCC相关通路。我们的研究结果表明,FBXL19-AS1不仅是HCC诊断和预后的潜在生物标志物,而且可能具有致癌功能。