The Regulatory Role of MicroRNA in Hepatitis-B Virus-Associated Hepatocellular Carcinoma (HBV-HCC) Pathogenesis - PubMed (original) (raw)
Review
The Regulatory Role of MicroRNA in Hepatitis-B Virus-Associated Hepatocellular Carcinoma (HBV-HCC) Pathogenesis
Kurt Sartorius et al. Cells. 2019.
Abstract
The incidence and mortality of hepatitis B virus (HBV)-associated hepatocellular carcinoma (HBV-HCC) is an intractable public health problem in developing countries that is compounded by limited early detection and therapeutic options. Despite the early promise of utilizing the regulatory role of miRNA in liver cancer, this field remains largely in the work-in-progress phase. This exploratory review paper adopts a broad focus in order to collate evidence of the regulatory role of miRNA in each stage of the HBV-HCC continuum. This includes the regulatory role of miRNA in early HBV infection, chronic inflammation, fibrosis/cirrhosis, and the onset of HCC. The paper specifically investigates HBV dysregulated miRNA that influence the expression of the host/HBV genome in HBV-HCC pathogenesis and fully acknowledges that this does not cover the full spectrum of dysregulated miRNA. The sheer number of dysregulated miRNA in each phase support a hypothesis that future therapeutic interventions will need to consider incorporating multiple miRNA panels.
Keywords: HBV-HCC continuum; dysregulated; hepatitis B infected hepatocellular carcinoma; miRNA; regulatory; role.
Conflict of interest statement
The authors declare no conflicts of interest.
Figures
Scheme 1
HBx-mediated miRNA pathways in early/chronic HBV infection. CCL22: C-C motif chemokine 22; SOCS1: Suppressor of cytokine signaling 1; C/EBP: CCAAT/enhancer-binding protein; HO1: heme oxygenase 1; CREB: c-AMP-response element binding protein.
Scheme 2
Inflammation pathways in HBV-induced pathways. HSC: hepatocyte stellate cell; TLR: toll-like receptor; TNF: tumor necrosis factor; NK: natural killer cells; TRAIL: TNF-related apoptosis-inducing ligand; TAK1: transforming growth factor beta-activated kinase 1; IKKβ: inhibitor of NFκB kinase.
Scheme 3
HBx-induced miRNA in inflammation pathways. TLR: toll-like receptor; IRAK1: interleukin-1 receptor associated kinase 1; TRAF6: tumor necrosis factor receptor associated factor 6; IL: interleukein; STAT3: signal transducer and activator of transcription 3; PTEN: phosphatase and tensin gene; PDCD4: programmed cell death protein 4 gene.
Scheme 4
HBx-mediated fibrosis/cirrhosis pathways. TGFβ: transforming growth factor beta; RICTOR: rapamycin-insensitive companion of mammalian target of rapamycin; RHEB: Ras homolog enriched in brain; HSC: hepatocyte stellate cells; ECM: extracellular matrix; ZEB1/2: zinc finger E-box-binding homeobox1/2.
Figure 1
HBx-dysregulated miRNA in the P13K/MAPK liver cancer pathway. HBV-specific abbreviations include endothelin-1 (Edn-1), HIST METH (histone methylation), Farnesoid X receptor (FXRα).
Figure 2
Dysregulated miRNA in the WNT/β-catenin liver cancer pathway. HBV-specific abbreviations DCC6 (DCC-adaptor protein), DNA METH (DNA methylation), HISTONE METH ((histone methylation), PPARγ (peroxisome proliferator-activated receptor gamma), EMT (epithelial mesenchymal transition).
Figure 3
Dysregulated miRNA in the TP53 liver cancer pathway. HBV-specific abbreviations include DNA METH (DNA methylation), HISTONE METH (histone methylation).
Figure 4
Dysregulated miRNAs in the JAK/STAT liver cancer pathway. METH (Methylation) C/EBP (CCAAT/enhancer-binding protein) Enh11 (enhancer 11).
References
- Cancer I.A.f.R.O. World Health Organization. Globocan 2012: Estimated cancer incidence, mortality and prevalence worldwide in 2012. [(accessed on 1 September 2014)]; Available online: http://globocan.iarc.fr/Pages/fact_sheets_cancer.Aspx.
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