Analysis of long non-coding RNA (lncRNA) expression in hepatitis B patients

Abstract

Long non-coding RNAs (lncRNAs) have been implicated in numerous biological processes, including epigenetic regulation, cell-cycle control, and transcriptional/translational regulation of gene expression. Differential expression of lncRNAs and disruption of the regulatory processes are recognized as critical steps in cancer development. The role of lncRNAs in hepatitis B virus (HBV) infection is not well understood. Here we analyzed the expression of 135 lncRNAs in plasma samples of 82 HBV patients (classified as chronic patients, inactive carriers, or resolved patients) at diagnosis and at 12 months of treatment in relation to control group (81 healthy volunteers). We also investigated the effect of small interfering RNA (siRNA)-mediated silencing of lincRNA-SFMBT2 on HBV-positive human liver cancer cell line. lncRNA expression was analyzed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Chemically synthesized siRNAs were transfected into the cell lines using Lipofectamine 2000 Reagent (Thermo Fisher Scientific). HBV DNA and HBsAg and HBeAg were detected in transfected cultures by real-time PCR and ELISA, respectively, using commercial kits. We observed changes in lncRNA expression in all three HBV groups, compared to control group. Most notably, the expression of anti-NOS2A, lincRNA-SFMBT2, and Zfhx2as was significantly increased and expression of Y5 lncRNA was decreased in chronic HBV patients. A decreased Y5 expression and increased lincRNA-SFMBT2 expression were observed in inactive HBsAg carriers. The expression of HOTTIP, MEG9, and PCAT-32 was increased in resolved HBV patients, and no significant change in the expression of Y5 was observed, compared to control group. siRNA-mediated inhibition of lincRNA-SFMBT2 decreased the level of HBV DNA in human liver cancer cells. Further research is needed to confirm the prognostic as well as therapeutic role of these lncRNAs in HBV patients.

Long noncoding RNA GAS5 does not regulate HBV replication

“…Intriguingly, in a research conducted in Turkey which identified the expression profiles of lncRNAs in patients with hepatitis B, GAS5 was downregulated in CHB, inactive HBsAg carriers, and resolved patients with HBV compared with the healthy control group. However, after 12 months of treatment/follow‐up in all three patient groups, GAS5 significantly increased . The inconsistency here, which might be caused by different HBV virus genotypes or ethnic heterogeneities of the patients, needed to be explored in further studies.…”

Differential expression profile of long noncoding RNAs in chronic HBV infection: New insights into pathogenesis

“…Previously, Yilmaz Susluer et al 18 applied qRT‐PCR to analyze the expression of 135 lncRNAs in plasma from 82 patients with chronic HBV infection (classified as chronic patients, inactive carriers, or resolved patients) and 81 healthy volunteers. Compared with healthy controls, they identified 15 upregulated and 7 downregulated lncRNAs from initial diagnosis to the 12th month of treatment/follow‐up in patients with chronic HBV infection.…”

Long noncoding RNAs: Novel regulators of virus‐host interactions

“…Peng and colleagues have analyzed the lung transcriptome in severe acute respiratory syndrome‐associated coronavirus (SARS‐CoV)‐infected mice and reported that the expression of 504 annotated and 1406 unannotated lncRNAs had significant changes . In addition, other viral families, such as Zika virus, hepatitis B virus (HBV), and hepatitis C virus, have been shown upon host infection to lead to differential expression of host lncRNAs compared with uninfected controls. Therefore, the differential expression of lncRNAs in various cell types following viral infection appears to be a widespread phenomenon and not a property attributable to one viral family or host target cell.…”