LncRNA HOTAIR modulates hepatitis B virus transcription and replication by enhancing SP1 transcription factor
LncRNA HOTAIR modulates hepatitis B virus transcription and replication by enhancing SP1 transcription factor
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LncRNA HOTAIR 通过增强 SP1 转录因子调节乙型肝炎病毒转录和复制
DOI：
10.1042/cs20200970
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发表时间：
2020-11-01
期刊：
影响因子：
6
通讯作者：
Yang, Xiao
中科院分区：
文献类型：
--
作者：
Ren, Fang;Ren, Ji-Hua;Yang, Xiao
B型肝炎病毒（HBV）感染仍然是一个全球性的公共卫生问题。全世界有近2.57亿人感染HBV，每年有88.7万人死于慢性B型肝炎（CH B）引起的肝硬化或肝癌。因此，迫切需要鉴定抗HBV的新靶点。长链非编码RNA（longnoncodingRNAs，LncRNAs）由于在肿瘤、炎症等疾病中的作用，近年来受到广泛关注。值得注意的是，已经发现越来越多的lncRNA在HBV发展中起作用。在本研究中，我们首先鉴定了一种著名的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例CHB患者中评估了HOTAIR的临床相关性，发现HOTAIR表达水平较高与ALT/AST水平较高相关，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的水平来提高HBV启动子的活性，从而促进HBV的转录和复制。结论：HOTAIR的表达与HBV的临床病理和生理特征相关。因此，HOTAIR可以作为一种新的HBV诊断和治疗生物标志物的基础上，它的能力，以促进HBV的转录和复制。
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.