[Frontiers in Bioscience, Landmark, 20, 78-104, January 1, 2015]

The role of circulating microRNA in hepatocellular carcinoma

Simon Chang-Hao Tsao 1, 2 , Andreas Behren 2 , Jonathan Cebon 2 , Christopher Christophi 1

1The University of Melbourne, Department of Surgery Austin Health, Studley Road, Heidelberg, Victoria, Australia 3084, 2The Ludwig Institute for Cancer Research, Level 5, Olivia Newton-John Cancer and Wellness Centre, Austin Health, 145-163 Studley Road, Heidelberg, Victoria, Australia 3084

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Search Strategy
4. Circulating miRNA
    4.1. miR-18a
      4.1.1. Tissue
      4.1.2. Serum
    4.2. miR-92a
      4.2.1. Tissue
      4.2.2. Serum
    4.3. miR-26a
      4.3.1. Tissue
      4.3.2. Serum
    4.4. miR-221
      4.4.1. Tissue
      4.4.2. Serum
    4.5. miR-224
      4.5.1. Tissue
      4.5.2. Serum
    4.6. miR-500
      4.6.1. Tissue
      4.6.2. Serum
    4.7. miR-885-5p
      4.7.1. Tissue
      4.7.2. Serum
    4.8. miR-15b, -130b
      4.8.1. Tissue
      4.8.2. Serum
    4.9. miR-21
      4.9.1. Tissue
      4.9.2. Serum
    4.10. miR-223
      4.10.1. Tissue
      4.10.2. Serum
    4.11. miR-122
      4.11.1. Tissue
      4.11.2. Serum
    4.12. miR-16
      4.12.1. Tissue
      4.12.2. Serum
    4.13. miR-195, -199a
      4.13.1. Tissue
      4.13.2. Serum
    4.14. miR-21, -26a, -27a, -122, -192, -223, -801
      4.14.1. Tissue
      4.14.2. Serum
    4.15. miR-25, -375, let-7f
      4.15.1. Tissue
      4.15.2. Serum
5. Discussion
6. Acknowledgement
7. References

1. ABSTRACT

Hepatocellular carcinoma (HCC) is a rapidly progressing disease that exerts a huge burden on patients and health care systems. Rapid progression and difficulty in detecting early disease are major obstacles in offering potentially curative treatments. Besides the lack of effective chemo- or immunotherapy for advanced disease, there are currently no reliable tumor markers or imaging technologies that can accurately diagnose early HCC or predict disease progression. Since the discovery of microRNA (miRNA) and its involvement in hepatocarcinogenesis, the literature describes their usefulness as potential new biomarkers and treatment targets. Some of these miRNAs can also be found in the systemic circulation. With advances in detection and sequencing technologies, an increasing amount of data demonstrate the possibility of using circulating miRNAs as biomarkers to improve our current management of HCC in a less-invasive manner. This paper will review circulating miRNAs with a known function in HCC, describing their role and function in tumorigenesis. This review discusses their potential use as biomarkers in conjunction with emerging treatments in the diagnosis and targeting of this disease.

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Abbreviations: ADAM: A disintegrin and metalloprotease; AEG-1: Astrocyte elevated gene-1; AFP: Alpha-fetoprotein; AFP-L3: AFP Lens culinaris agglutinin-reactive fraction; API-5: Apoptosis inhibitor 5; AUC: Area under the operating characteristic curve; CD1: Cyclin D1; CDK2: Cyclin-dependent kinase 2; CDK6: Cyclin-dependent kinase 6, CTC: Circulating tumor cell, DCP: Des-gamma-carboxyprothrombin; EMT: Epithelial to mesenchymal transition; ERα: Estrogen receptor alpha; ESR1: Estrogen receptor 1; HBV: Hepatitis B virus; HCC: Hepatocellular Carcinoma; HCV: Hepatitis C virus; HSC: Hepatic stellate cells; IGF-1: Insulin like growth factor 1; IGF1R: Insulin-like growth factor 1 receptor; Let-7: Lethal-7; MCM5: mini-chromosome maintenance protein; MCM7: minichromosome maintenance protein 7; mTOR: Mammalian target of rapamycin; PIAS3: Protein Inhibitor of Activated Signal Transducer and Activator of Transcription 3; PTEN: Phosphatase and tensin homolog; SRF: Serum response factor; STAT: Signal transducer and activator of transcription; STAT3: Signal Transducer and Activator of Transcription 3; STMN1: Stathmin 1; VEGF: Vascular endothelial growth factor; YAP: Yes-associated protein.

Key Words: MicroRNA, Serum microRNA, Circulating microRNA, Hepatocellular carcinoma, HCC, Prognosis, Diagnosis, Therapy, Treatment, Review

Send correspondence to: Christopher Christophi, The University of Melbourne, Department of Surgery Austin Health Studley Road, Heidelberg, Victoria, Australia 3084. Tel:613-9496-5468, Fax: 613-945-8650, E-mail: c.christophi@unimelb.edu.au