The Key Laboratory of Molecular Biology of Infectious Diseases designated by the Chinese Ministry of Education, Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
Clinical Laboratory Medicine Center, Shenzhen Hospital, Southern Medical University, No.1333 Xinhu Road, Baoan District, Shenzhen 518100, P.R. China.
Clin Sci (Lond). 2020 Nov 27;134(22):3007-3022. doi: 10.1042/CS20200970.
Hepatitis B virus (HBV) infection remains a global public health problem. Nearly 257 million people worldwide have been infected with HBV, resulting in 887,000 people dying of cirrhosis or liver cancer caused by chronic hepatitis B (CHB) annually. Therefore, identification of new targets against HBV is urgently needed. Long noncoding RNAs (LncRNAs) have gained widespread attention in recent years due to their function in cancer, inflammation and other diseases. Notably, a growing number of lncRNAs have been found to play a role in HBV development. In the present study, we first identified a famous lncRNA, HOTAIR, which was significantly up-regulated in HBV-infected cells and PBMCs from CHB patients. Furthermore, we evaluated the clinical relevance of HOTAIR in 20 CHB patients and found that higher levels of HOTAIR expression were associated with higher ALT/AST levels and were positively correlated with HBsAg and HBV DNA levels. In addition, functional analysis showed that HOTAIR promoted HBV transcription and replication by elevating the activities of HBV promoters via modulation of the levels of cccDNA-bound SP1. In conclusion, our study reveals that HOTAIR expression is correlated with the clinicopathological and physiological characteristics of HBV. Thus, HOTAIR may serve as a novel HBV diagnostic and therapeutic biomarker based on its ability to facilitate HBV transcription and replication.
乙型肝炎病毒 (HBV) 感染仍然是一个全球性的公共卫生问题。全球有近 2.57 亿人感染了 HBV，每年有 88.7 万人死于由慢性乙型肝炎 (CHB) 引起的肝硬化或肝癌。因此，迫切需要确定针对 HBV 的新靶点。近年来，长链非编码 RNA (lncRNA) 因其在癌症、炎症和其他疾病中的功能而受到广泛关注。值得注意的是，越来越多的 lncRNA 被发现在 HBV 的发展中发挥作用。在本研究中，我们首先鉴定了一个著名的 lncRNA，HOTAIR，它在 HBV 感染的细胞和 CHB 患者的 PBMC 中显著上调。此外，我们在 20 名 CHB 患者中评估了 HOTAIR 的临床相关性，发现 HOTAIR 表达水平越高，ALT/AST 水平越高，与 HBsAg 和 HBV DNA 水平呈正相关。此外，功能分析表明，HOTAIR 通过调节 cccDNA 结合的 SP1 水平，提高 HBV 启动子的活性，从而促进 HBV 的转录和复制。总之，我们的研究表明，HOTAIR 的表达与 HBV 的临床病理和生理特征相关。因此，HOTAIR 可能成为一种新型的 HBV 诊断和治疗生物标志物，因为它能够促进 HBV 的转录和复制。
