Alexander Le

Introduction. Hepatocellular carcinoma (HCC) represents the fourth leading and fastest rising cause of cancer death worldwide, with over 800,000 new cases and one million people dying from HCC annually.¹ Hepatitis B virus (HBV) infection and chronic hepatitis incidence are strongly associated with the development of hepatocarcinogenesis.¹ Long non-coding RNA (lncRNA) are RNA transcripts longer than 200 nucleotides that are not translated into proteins.² lncRNAs can regulate gene expression as well as the proliferation, migration, and invasion of HCC cells.¹ The presence of hepatitis B virus protein X (HBx), encoded by the HBV gene, can regulate the expression of HCC-related lncRNAs.¹ Numerous lncRNAs have been shown to be deregulated in the course of HBV infection and HCC development.³ Further exploring the role of lncRNAs in relation to HBV-related HCC has implications for future therapeutic targeting and diagnostics.² Methods. Researchers developed lentiviral vectors expressing the HBx gene to be transfected into HepG2 and HBx-HepG2 cells to measure lncRNA-ATB expression.⁴ Expression of the lncRNA n335586 was compared between isolated HBV (+) and HBV (-) HCC tissues.⁵ An lncRNA microarray analysis was performed on H11, which inhibits hepatitis B virus (HBV) replication.⁶ Using pathway analyses and Gene Ontology, researchers generated and analyzed the profiles of various differentially expressed lncRNAs and mRNAs.⁶ DLEU2 is an lncRNA expressed in the liver and increased in HCC. Researchers modeled various DLEU2-HBx protein complexes via structural bioinformatics tools.⁷ Results. lncRNA-ATB expression was upregulated in HBx-HepG2 cells.⁴ lncRNA n335586 expression was significantly increased in HBV (+) HCC tissues.⁵ H11 was revealed to inhibit HBV replication by regulating the β-catenin, Wnt, and PPAR signaling pathways.⁶ Researchers found that various lncRNAs and mRNAs are involved in RNA-mediated post-transcriptional gene silencing, regulation of viral genome replication, and Jak-STAT signaling and apoptosis pathways.⁶ Results confirmed the ability of HBx to bind RNA and establish epigenetic control of both viral cccDNA and host genes.⁷ Conclusions. Current therapeutic options for patients experiencing HBV-related hepatocellular carcinoma are limited. However, targeting lncRNAs has shown to be possible therapeutic strategies for stymieing the development and progression of this disease at the molecular level. The ability of some lncRNAs to modulate transcription and impact various signaling and apoptotic pathways has shown promise. Further research on the interaction between HBx and associated lncRNAs, such as DLEU2, can provide greater insight into the development of hepatocellular carcinoma linked to patients infected with the hepatitis B virus.

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