Poster Presentation 28th Lorne Cancer Conference 2016

Hormonally driven microRNAs as a key regulatory mechanism of the mismatch repair gene MSH2 in prostate cancer (#207)

Patrick J McCoy 1 2 3 , Michael Clarkson 1 2 3 , Ryan Stuchbery 1 2 3 , Andrew Ryan 4 , Niall Corcoran 1 2 3 , Chris Hovens 1 2 3
  1. Victorian Comprehensive Cancer Centre, Melbourne, Victoria, Australia
  2. University of Melbourne, Melbourne, Victoria, Australia
  3. Australian Prostate Cancer Research Centre Epworth, Melbourne, Victoria, Australia
  4. Tissupath Specialist Pathology Services, Melbourne, Victoria, Australia

BACKGROUND: Lynch syndrome is the most common hereditary cancer syndrome and is caused by a defect in one of four DNA mismatch repair genes (MSH2, MLH1, PMS2 and MSH6). Prostate cancer is not considered to be a lynch syndrome associated cancer but recent studies have identified that patients with a defect in the MSH2 gene have a significantly higher chance of developing prostate cancer. However, this is not observed with patients who have a defect in MLH1, PMS2 or MSH6. In this study we have investigated the potential for post-transcriptional regulation of MSH2 by microRNAs and the role androgens and estrogens have in microRNA regulation in prostate cancer.

 

 

AIMS:

1.      To investigate MSH2 loss in a patient cohort and identify the expression profiles of two microRNAs, miR-21 and miR-212.

2.      Use western blot analysis to prove miR-21 and miR-212 target MSH2 and reduce its expression in prostate cancer cell lines.

3.      Use cell based assays to define the affect of androgens and estrogens on the expression of miR-21 and miR-212.


METHODS and RESULTS: Immunohistochemistry (IHC) was performed on a cohort of 99 recurrent and 90 non-recurrent prostate cancer patients to investigate the presence of the MSH2 protein. We found that 6 of our recurrent patients had no staining, whereas all non-recurrent patients showed at least partial staining. Additionally, 23 recurrent patients and only 5 non-recurrent patients were observed to have weaker MSH2 staining in their cancer compared to the patient’s benign tissue. MiR-21 and miR-212 were confirmed to target the MSH2 protein by western blot analysis. QPCR was performed on these patient samples to identify the expression profile of miR-21 and miR-212. Hormonal regulation of miR-21 and miR-212 was confirmed after treatment with a panel of androgens and estrogens.