RNA Splicing Variants Linked To Aggressive Prostate Cancer in African Americans

MedicalResearch.com Interview with:

Dr. Norman Lee PhD Professor of Pharmacology and Physiology School of Medicine and Health Sciences George Washington University

Dr. Lee

Dr. Norman Lee PhD
Professor of Pharmacology and Physiology
School of Medicine and Health Sciences
George Washington University

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: There are health disparities when it comes to prostate cancer. The African American population, in general, has a higher prostate cancer incidence and mortality rate compared to other racial groups such as European Americans. A major reason for this disparity is due to socioeconomic factors such as access to health care. There are also biological influences for the disparities, such as specific gene mutations and genetic polymorphisms that are found at a higher incidence in the African American population.

My lab has been studying other potential contributing biological factors in prostate cancer disparities; namely, RNA splicing. RNA splicing is a cellular program that increases the diversity of expressed proteins by regulating which exons are included in an mRNA transcript, leading to mRNA variants encoding slightly different proteins (or isoforms) in different cells, organs, and individuals. One can think of RNA splicing as a form of genetic diversity. What we have found is that the repertoire of mRNA variants can differ in prostate cancer between African and European Americans. We also find that the mRNA variants in African American prostate cancer encode signal transduction proteins that are more oncogenic and resistant to targeted therapies, compared to the variants found in European American prostate cancer.

MedicalResearch.com: What should clinicians and patients take away from your report?

Response: There is a complex interaction between socioeconomic and biological factors at ‘play’, resulting in cancer health disparities. We have identified RNA splicing as an additional biological component. Differences in RNA splicing between patients appears to have a significant impact on tumor aggressiveness and therapeutic responsiveness.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: In the age of precision medicine, our study also illustrates the importance of knowing beforehand, not only existing mutations, but also the mRNA variants in the tumor. Protein isoforms encoded by specific splice variants can lead to tumors that are unresponsive to the currently available targeted therapies. This is a mechanism for drug resistance that needs to be fully investigated as it pertains to cancer therapy development. In terms of future directions, we are applying our findings in African American prostate cancer to other cancers, specifically we are looking at whether or not some of the novel mRNA variants discovered in African American prostate cancer may also play a role in resistance to targeted therapies in other types of cancers, such as non-Hodgkin Lymphoma.

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Bi-Dar Wang, Kristin Ceniccola, SuJin Hwang, Ramez Andrawis, Anelia Horvath, Jennifer A. Freedman, Jacqueline Olender, Stefan Knapp, Travers Ching, Lana Garmire, Vyomesh Patel, Mariano A. Garcia-Blanco, Steven R. Patierno, Norman H. Lee. Alternative splicing promotes tumour aggressiveness and drug resistance in African American prostate cancer. Nature Communications, 2017; 8: 15921 DOI: 1038/ncomms15921 

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