Role of miRNA-126 in Hepatocellular Carcinoma and Cholangiocellular Carcinoma

  • Author / Creator
    Zailaie,Samar A
  • Hepatocellular carcinoma (HCC) and Cholangiocellular Carcinoma (CCA) represent the most common malignant tumor of the liver accounting about 90 % of all liver malignancies. The overall prognosis of HCC and CCA is very poor due to the lack of effective treatment. MicroRNAs (miRNAs) represent a small endogenous non-coding RNAs that play a significant role in the regulation of gene expression post-transcriptionally. Altered expression of miRNAs has been observed in many malignancies including liver cancer. However, the expression level of miR-126 in HCC and CCA and its role in hepatic-carcinogenesis remains unclear. This thesis aimed to study the expression level, localization and biological significance of miRNA-126 in HCC and CCA. In an effort to distinguish the expression pattern of miR-126 in HCC and CCA tissues and cell lines, two expression analysis has been used: in situ hybridization (ISH) and quantitative real time polymers chain reaction (QRT-PCR). Our ISH analysis has shown a significant reduction in miR-126 level in HCC and CCA tissues relative to their corresponding normal tissues. Moreover, an intensive expression of miR-126 in normal hepatocyte, blood vessels and sinusoid cells has been observed. Our qRT-PCR data demonstrated a lower expression level of miR-126 in HCC and CCA cell lines relative to a normal kidney cell line. By using several gain of functions analysis, this study demonstrated the effect of miR-126 in HCC and CCA cell lines. The over-expression of miR-126 in HepG2 and HuccT1 has significantly inhibited cell proliferation and growth. On the other hand, our data has shown that miR-126 overexpression inhibited cell ability to migrate. Taken together, this study indicted that miR-126 could play a critical role in hepatic carcinogenesis. Indeed, miR-126 may serve as a novel suppressive miRNA in liver cancer. Furthermore, miR-126 may serve as potential therapy, diagnostic and prognostic biomarker.

  • Subjects / Keywords
  • Graduation date
  • Type of Item
  • Degree
    Master of Science
  • DOI
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
  • Language
  • Institution
    University of Alberta
  • Degree level
  • Department
    • Laboratory Medicine and Pathology
  • Specialization
    • Molecular Pathology
  • Supervisor / co-supervisor and their department(s)
    • Dr. Consolato Sergi , Departmnet of Laboratory Medicine and Pathology
    • Dr.Judith Hugh , Departmnet of Laboratory Medicine and Pathology
  • Examining committee members and their departments
    • Dr. Xing-Zhen , Departmnet of Physiology
    • Dr.Fiona Bamforth , Departmnet of Laboratory Medicine and Pathology