research - Associated Student Government, Northwestern University

ABSTRACTTargeting MircoRNA-21 forTherapy Against Prostate CancerProgression and MetastasisJames LeeBIOLOGICAL SCIENCES PROGRAMMOLECULAR PHARMACOLOGY AND BIOLOGICAL CHEMISTRYMing ZhangFACULTY ADVISORMOLECULAR PHARMACOLOGY AND BIOLOGICAL CHEMISTRYFEINBERG SCHOOL OF MEDICINEIntroductionWith its ability to affect every organ and tissuethrough various mechanisms, cancer is one of the mostcomplex diseases that we face. Prostate cancer is themost prevalent cancer in men; one in six men will bediagnosed with prostate cancer during his lifetime, andone in thirty-six men will die of the disease. 1,2 The roleof microRNA-21 (mir-21) in prostate cancer has notbeen clearly defined yet, and the goal of this experimentis to investigate how mir-21 affects prostate cancer progressionand metastasis (invasion of other organs). Understandingits role might be a key in designing a newtherapeutic approach to prostate cancer.BackgroundMicroRNAs (miRNA) regulate gene expression bydegrading messenger RNA (mRNA) that encode forproteins. 3,4 A single miRNA molecule can interact withas many as hundreds of target mRNAs and can thereforeorchestrate many different pathways at once to elicit abroader cellular response. 3,4 A few of these modulatorsare deregulated in cancer, making miRNA a potentialtarget for therapy. 3Cancer results from multiple perturbations of differentgenes and proteins. 3 Within this context, miRNAsserve as pivotal centers, capable of concurrently regulatingnetworks of related processes in cancer progressionand metastasis (figure 1). 3,5 Considering this uniqueability of miRNA, miRNA-mediated cancer therapywill be more comprehensive than therapy targetingindividual genes or proteins. 3 Also, miRNA’s specificityVOLUME 7, 2011-2012for mRNA sequences make miRNA treatment more effectivethan current chemotherapy that affects normalcells. 3 Mir-21 is one of the miRNAs deregulated in cancer. 5Its over-expression is correlated with tumor growth, butits mechanism is not yet understood. 5 Understandingmir-21’s role in prostate cancer can help develop a therapeuticapproach targeting mir-21-mediated pathways.Previous research suggests that transforming growthfactor beta (TGF-β) and Ras, two proteins involved incancer, activate mir-21. 4,5 In prostate cancer, Ras activationand aberrant TGF- β activity play significant rolesin tumor progression, suggesting a relationship betweenthese proteins and mir-21. 5,6 Also, maspin, a keytumor suppressor, is believed to be downregulated bymir-21, contributing to tumor proliferation and invasion.2,7,8,9,10,11 Therefore I hypothesize that TGF- β andRas induce mir-21 expression in prostate cancer. This inturn silences maspin, subsequently leading to prostatecancer progression and metastasis.MethodFirst, the relationship between mir-21 and maspinwill be investigated. Prostate cancer cells will betreated with anti-mir-21 that inhibits mir-21. Anti-mir-21-treated cells with low mir-21 will be compared withuntreated cells with high mir-21 for maspin expression.Then, to investigate the effect of mir-21 on tumorcharacteristics, assays that investigate cell proliferation,migration, and invasion will be conducted with cells expressinghigh vs. low mir-21 levels. Subsequently, to fur-NORTHWESTERN UNDERGRADUATE RESEARCH JOURNAL39