Science University Research Symposium (SURS)
Investigating the Role of KMT2A in Rhabdoid Tumorigenesis Utilizing CRISPRi-Mediated Knockdown
Publication Date
2024
College
Sciences and Mathematics, College of
Department
Biology, Department of
SURS Faculty Advisor
Andrea Florian
Presentation Type
Poster Presentation
Abstract
KMT2A (also known as MLL1) is a histone methyltransferase, most known for its role in gene regulation. KMT2A modifies gene transcription by methylating histone H3 at lysine 4 (H3K4), which markedly decreases transcription initiation. Dysregulation of KMT2A occurs primarily due to chromosomal translocations, which are associated with cancers such as leukemia. Considering the important role KMT2A holds in these cancers, we decided to explore its role in the development of Rhabdoid Tumors. In this study, we used CRISPR interference (CRISPRi) with a single guide RNA (sgRNA) to selectively inhibit KMT2A transcription in Rhabdoid Tumor cells. We hypothesize that the downregulation of KMT2A will lead to a significant reduction in the proliferation of Rhabdoid Tumor cells. This work could establish KMT2A as an important driver mutation in Rhabdoid tumorigenesis, opening up new targets for chemotherapeutic treatments of Rhabdoid cancers.
Recommended Citation
Florian, A. C., Woodley, C. M., Wang, J., Grieb, B. C., Slota, M. J., Guerrazzi, K., Hsu, C. Y., Matlock, B. K., Flaherty, D. K., Lorey, S. L., Fesik, S. W., Howard, G. C., Liu, Q., Weissmiller, A. M., & Tansey, W. P. (2022). Synergistic action of WDR5 and HDM2 inhibitors in SMARCB1-deficient cancer cells. NAR Cancer, 4(1), Article zcac007. https://doi.org/10.1093/narcan/zcac007 Rao, R. C., & Dou, Y. (2015). Hijacked in cancer: The KMT2 (MLL) family of methyltransferases. Nature Reviews Cancer, 15(6), 334-346. https://doi.org/10.1038/nrc3929 Candoni, A., & Coppola, G. (2024). A 2024 update on menin inhibitors: A new class of target agents against KMT2A-rearranged and NPM1-mutated acute myeloid leukemia. Hematology Reports, 16(2), 244–254. https://doi.org/10.3390/hematolrep16020024
