Home / Research Supervisor Connect / Opportunity details

Characterization of ARL6IP5, PTPLB, and NIN in liver cancer

Summary

This project aims to investigate the possible role of ARL6IP5, PTPLB, and NIN in human liver cancer

Supervisor(s)

Dr Liang Qiao, Professor Jacob George

Research Location

Westmead - Westmead Millennium Institute

Program Type

PHD

Synopsis

Liver cancer is a prime example of inflammation-related malignancy. Hepatitis B virus (HBV) is the major cause of liver cancer in Asian and African countries whereas hepatitis C virus (HCV) is the cause for most liver cancer cases in Western countries, including Australia. The combined incidence of HBV- and HCV-infection related liver cancer accounts for more than 75% of all HCC cases worldwide. Hence, HBV and HCV are the most important causes for liver cancer. Currently, more than 170 million people worldwide (3% of the world population) are chronically-infected with HCV. Liver cirrhosis may develop in some HCV infected individuals over a course of 15-40 years, and 3.5% of whom developed liver cirrhosis will go on to develop liver cancer. Despite numerous studies, the precise mechanisms of how these viral factors cause liver cancer have not yet been fully clarified. What is certain, however, is that multiple molecular pathways may be interacting during the development of liver cancer following long-term viral infections.
Using a microarray technique, we recently analyzed the gene expression profile in the mononuclear cells isolated from the peripheral blood of patients infected with HCV. We have found three genes are significantly and specifically expressed in HCV infected individuals. These genes are ARL6IP5 (p<0.0002), NIN (Ninein gene) (P<0.005), and PTPLB genes (p<0.002). These three biomarker genes are highly functionally important. The ARL6IP5 gene encodes for protein PRA1 family protein 3 in humans. The encoded protein of ARL6IP5 is associated with the proper function of cytoskeleton and regulation of cell differentiation. Recently it was shown that ARL6IP5 is significantly associated with local aggressiveness and metastatic behavior of several soft tissue tumors. The NIN (Ninein) gene is important for centrosomal function in epithelial cells, such as the positioning and anchoring of the microtubules. The PTPLB gene (protein tyrosine phosphatase-like, member b1) is a 254 amino acid protein localizing in the endoplasmic reticulum membrane. This protein may be involved in the regulation of ER-associated degradation process. As HCV is such a strong carcinogenic agent for liver carcinogenesis, and these three genes are differentially expressed at such a higher level in HCV infected subjects, we speculate that these three genes are mechanistically related to the development of HCV related liver diseases including liver cancer. However, solid laboratory evidence is needed to support such a presumption.
Thus, in this project, we will characterize the expression and function of these genes in liver cancer.

Additional Information

Culture of human HCC cell lines;
     Gene expression analysis in HCC and matched normal hepatic tissues by real time PCR (qPCR) and Western blot;
     Construction of tissue microarray.
     Basic molecular biological techniques such as extraction of total RNA and protein from cultured cells and tissues; reverse transcription of RNA to cDNA; quantitation of RNA and protein; qPCR; cDNA cloning; vector construction; bacterial transformation; plasmid purification; sub-cloning; transfection of cells with siRNA and plasmids; Western Blotting.
     Other cell biology techniques: histology, immunohistochemistry; light and fluorescence microscopy; cell proliferation assay; apoptosis assay; migration assay; etc.

About the Storr Liver Unit
The Western Clinical School's Storr Liver Unit investigates the pathogenesis of liver disease, and the diverse causes of liver injury, such as drugs and toxins, metabolic factors and viruses. Internationally acclaimed, the Unit has made substantial contributions to defining how the liver responds to injury, and how genes involved in the metabolisms of drugs and toxic products of liver metabolism are regulated.
Liver cancer is Australia's fastest growing cancer, and this is an opportunity to take a role in the research of this emerging health focus. The Unit is well funded and thus there is the opportunity to employed cutting edge techniques and tools to bring each project to fruition. Joining a successful research team with expertise in liver disease and cancer, there will also be opportunity to collaborate with internationally-renowned cancer researchers at the Westmead Millennium Institute. As part of the community of over 400 researchers based on the Westmead campus, there will be the possibility to utilise the Institute's state-of-the-art molecular, translational and cell biological facilities.

Want to find out more?

Contact us to find out what’s involved in applying for a PhD.

Contact Research Expert to find out more about participating in this opportunity.

Browse for other opportunities within the Westmead - Westmead Millennium Institute .

Keywords

Liver cancer, gene expression, HCV

Opportunity ID

The opportunity ID for this research opportunity is: 1316

Other opportunities with Dr Liang Qiao

Other opportunities with Professor Jacob George