Poster abstracts

Poster number 45 submitted by Omid Gholamalamdari

lincNXT1 modulates basal-like breast cancer invasiveness through regulating the expression of THBD

Omid Gholamalamdari (Department of Cell and Developmental Biology, UIUC), Deepak Singh (Department of Cell and Developmental Biology, UIUC), Tina Moazezi (Department of Cell and Developmental Biology, UIUC), Supriya G. Prasanth (Department of Cell and Developmental Biology, UIUC), Jian Ma (Computational Biology Department, CMU), Kannanganattu V. Prasanth (Department of Cell and Developmental Biology, UIUC)

Abstract:
Genome Wide Association Studies have identified genomic regions associated with different traits, including cancer. Interestingly 88% of these regions falls in noncoding portion of genome. In addition to regulatory elements, long non-coding RNAs(lncRNAs) are present in these regions. lncRNAs have been shown to play regulatory roles in different cellular processes including cell cycle, genome imprinting, nuclear organization, cell fate, development, and signaling. High-throughput RNAseq data reveal that the expression of lncRNAs is spatiotemporally regulated, and is dysregulated in cancers, including basal-like breast cancer. However, roles of lncRNAs in basal-like breast cancer are largely unknown. Here we have identified lncRNAs with potential cis regulatory function in basal-like breast cancer. We’ve characterized lincNXT1 as a cis regulator of Thrombomodulin (THBD) in basal-like breast cancer. Our results indicate that lincNXT1 levels are positively correlated with THBD mRNA in basal-like patients. lincNXT1 downregulation decreases cellular THBD levels, and therefore adhesion properties of cells and increases migrative and invasive properties of basal-like mammary epithelial cells. We anticipate our results pave the road for better diagnostic tools and targeted therapies in basal-like breast cancer.

References:
1. Esteller, M. (2011) Non-coding RNAs in human disease. Nat. Rev. Genet.
2. Quinodoz, S. & Guttman, M. (2014) Long noncoding RNAs: an emerging link between gene regulation and nuclear organization. Trends Cell Biol.
3. Tripathi, V., Ellis, J., Shen, Z., Song, D. & Pan, Q. (2010) The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation. Mol. Cell.
4. Xing, Z., Lin, A., Li, C., Liang, K., Wang, S., Liu, Y., Park, P. K., et al. (2014) lncRNA Directs Cooperative Epigenetic Regulation Downstream of Chemokine Signals. Cell
5. Hindorff, L., MacArthur, J., Morales, J. & Junkins, H. (2014) A Catalog of Published Genome-Wide Association Studies.

Keywords: Long non-coding RNA, Basal-like breast cancer, THBD