Increased Cyclin D1 (CCND1) Protein Is Associated with Reduced MIR-193B Levels in Melanoma: A Potential Melanoma Regulatory Pathway
C Garady, J Chen, S Virk, H Feilotter, V Tron. Queen's University, Kingston, ON, Canada
Background: Cutaneous melanoma is an aggressive form of human skin cancer characterized by high metastatic potential and poor prognosis. Emerging evidence suggests that microRNA dysregulation may play a role in melanoma development. In our initial study, we found miR-193b is downregulated in malignant melanomas relative to benign nevi. Furthermore, our functional studies demonstrated that miR-193b might regulate cell proliferation by downregulating expression of cyclin D1 in melanoma cell lines.
Design: We speculated that the downregulation of miR-193b level might contribute to the upregulation of cyclin D1 in melanoma. To confirm this, we assessed cyclin D1 level on a TMA comprised of 8 benign nevi, 7 primary melanomas and 8 metastatic melanomas using immunohistochemical staining. The scanned TMA image was scored for intensity of staining by Aperio's Immunohistochemistry image analysis. The miR-193b levels in those melanocytic tissues were examined in our previous microarray study. We compared the miR-193b expression levels to the percentage of positive nuclei for cyclin D1.
Results: The percentage of positive nuclei of staining for Cyclin D1 is upregulated from benign nevi (9.53 ± 3.62%) to primary melanomas (24.22±9.47%) and metastatic melanomas (37.88±7.85%) while miR-193b expression is downregulated from benign nevi (583.08±50.66) to primary melanomas (230.55±75.31) and metastatic melanomas (160.60±36.11). Regression analysis confirmed a weak negative correlation (R = - 0.45).
Conclusions: Our TMA validation study appears to support our hypothesis that miR-193b repress cyclin D1. Because miR-193b appears to have anti-proliferative effects in melanoma cells, it may have potential as a novel diagnostic and therapeutic tool. Our future direction will be to examine a larger melanoma sample set to test the correlation of miR-193b and cyclin D1.
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 65, Monday Morning