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.
Highlights
Hepatitis B virus (HBV) is a double-stranded DNA virus and a member of the Hepadnavirus family
The expression of 7 Long non-coding RNAs (lncRNAs) was decreased more than 2 fold at 12 months of treatment/follow-up compared to the expression values at the initial diagnosis, and in relation to control group (p < 0.05)
The expression of AK023948 was significantly downregulated in majority of papillary thyroid carcinomas (PTC) [22]
Summary
Hepatitis B virus (HBV) is a double-stranded DNA virus and a member of the Hepadnavirus family. HBV infection can lead to acute and chronic diseases of the liver and represents a global public health problem. Liver diseases associated with HBV are among the most common causes of liver transplantation [1]. The majority of the identified lncRNAs are transcribed by RNA polymerase II. It is assumed that lncRNAs are more numerous than protein-coding genes in the genome, accurate/complete classification and identification schemes for lncRNAs are still not available. Based on their location in relation to protein-coding genes, lncRNAs can be classified as intergenic, sense and antisense (exonic, intronic or overlapping), and bidirectional [5]. LncRNAs may be classified as RNAs that: 1) regulate gene expression, 2) act as microRNA (miRNA) decoys to free target mRNAs, 3) regulate mRNA translation, and 4) regulate protein activities [6]
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