Ghrelin antisense genes in lung cancer

Overview

Topic status: We're looking for students to study this topic.

Lung cancer metastasis is the most common cause of cancer deaths in the world for both men and women. The incidence of lung cancer is rising with the aging population and indigenous Australians are over-represented among lung cancer patients. While there have been improvements in its diagnosis and treatment, survival rates are still extremely poor, with only 15% of patients surviving within 5 years of diagnosis. At least 50% of patients are diagnosed when their disease is advanced. There are limited treatment options for advanced disease and metastatic disease is currently incurable. New therapeutic approaches to lung cancer are, therefore, urgently required. We have recently discovered a natural antisense gene, termed GHSROS (growth hormone secretagogue receptor opposite strand), which is encoded on the antisense strand of the ghrelin receptor (GHSR) gene. GHSROS is transcribed into long, non-protein-coding natural antisense RNA, and we have shown that GHSROS is highly expressed in lung cancer compared to normal tissue, indicating that it may play an important regulatory role. Indeed, have demonstrated that overexpression of GHSROS in the A549 and NCI-H1299 lung cancer cell lines increases the rate of cell migration and proliferation, processes required for metastasis to occur, indicating that GHSROS plays a role in this process, which is a hallmark of cancer progression. A better understanding of the molecular biology of lung cancer is likely to define new molecular lung cancer cell types and allow the development of novel targeted therapeutics and prognostic markers for this disease. We hypothesise that our novel natural ghrelin receptor antisense long non-coding RNA (GHSROS) plays a role in important processes in lung cancer progression, including cell migration, invasion, proliferation and anchorage-independent growth. GHSROS is highly expressed in lung cancer and could have potential as a therapeutic target.

Approaches: Using lung cancer cell lines over-expressing GHSROS we will determine the role of this antisense gene in lung cancer migration, invasion and anchorage independent growth. We will investigate the signalling pathways involved using proteomics analysis and microarray analysis.

References:

  1. Seim, I., Carter, Herington, Chopin. Revised genomic structure of the human ghrelin gene and identification of novel exons, alternative splice variants and natural antisense transcripts. BMC Genomics, 2007. 8:298.
  2. Seim, I, Carter, Herington, Chopin. Complex organisation and structure of the ghrelin antisense strand gene GHRLOS, a candidate non-coding RNA gene. BMC Mol Biol, 2008. 9:95.
Study level
Honours
Supervisors
QUT
Organisational unit

Science and Engineering Faculty

Research area

Medical Sciences

Contact

Please contact the supervisor.