LncRNA HOTAIR modulates hepatitis B virus transcription and replication by enhancing SP1 transcription factor

Abstract

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 this study, we first identified a famous lncRNA, HOTAIR, which was significantly upregulated 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.

Long non-coding RNA CRNDE as potential biomarkers facilitate inflammation and apoptosis in alcoholic liver disease

“…The four lncRNAs HOTAIR1, MALAT1, MEG3 and H19 have been proved to be highly correlated with primary liver cancer [ 26 – 29 ]. Not only in liver cancer, but also in hepatitis B, the overexpression of lncRNA-HOTAIR has recently been found to have regular interaction with HBV and HCC [ 30 ]. In cirrhosis (such as PBC), the gene GAS5 was screened out, which was preliminarily confirmed to be a biological marker of primary biliary cirrhosis and has a broad clinical application prospect [ 31 ].…”

Integrated Analysis of Long Noncoding RNA Expression Profiles in Acute-on-Chronic Liver Failure

“…Accumulation studies have reported that many lncRNAs participate in the HBV propagation. For example, lncRNA HOTAIR can regulate transcription and replication of HBV through promoting SP1 transcription factor [ 42 ]. lncRNA PCNAP1 promotes HBV replication and accelerates hepatocarcinogenesis via miR-154/PCNA/HBV covalently closed circular DNA signaling pathways [ 43 ].…”

LncRNA: A Potential Target for Host-Directed Therapy of Candida Infection

“…Obaid et al demonstrated that HOTAIR played key roles in LPS-induced metabolic programming in macrophages by activating NF-kB [ 144 ]. Besides, HOTAIR was significantly upregulated during hepatitis B virus (HBV) infection and may promote virus transcription and replication by elevating the activities of HBV promoters [ 145 ]. Mechanistically, HOTAIR could facilitate the degradation of IκBα, an inhibitory molecule of the NF-κB complex, to induce the expression of proinflammatory genes such as IL-6 in macrophages [ 146 ].…”