Knockdown of Long Noncoding RNAs in Breast Cancer
Poster Mar 31, 2015
1 Jennii Luu, 2 Jesper Maag, 1 Yanny Handoko, 3 Richard Redvers, 3,4 Robin L. Anderson, 5 Maren M. Gross , 2 Marcel E. Dinger, and 1,3 Kaylene J. Simpson 1 Victorian Centre for Functional Genomics, Peter MacCallum Cancer Centre; 2 Genome Informatics, The Kinghorn Cancer Centre, The Garvan Institute of Medical Research; 3 Metastasis Research Laboratory, Peter MacCallum Cancer Centre, 4 Sir Peter MacCallum Department of Oncology, University of Melbourne;
Traditionally genetics has held a protein centric view with RNA seen as an intermediate step between DNA and protein. Recently, the emerging evidence of pervasive transcription throughout the genome has challenged this view1,2. Long noncoding RNAs (lncRNA) are selectively expressed during different cell cycles3 as well as transcribed differently in specific cell types4, which emphasizes their importance in regulating cell specification. lncRNAs can work on every stage of transcription from chromatin remodeling, controlling transcription to post-transcriptional processing through various mechanisms such as directly binding to transcription activation sites, working as decoys for transcript suppressors/activators or as guiding/scaffold molecules for chromatin remodeling complexes5.
Increasing numbers of studies have associated disease with lncRNAs. However, such studies have typically only focused on exploring the function of individual lncRNAs. In preliminary studies, we investigated the functional consequences of lncRNA knockdown in the breast cell lines MCF 10A and MDA-MB-231 using cell viability and morphology as readouts. Using high throughput siRNA screening protocols established in the Victorian Centre for Functional Genomics, we have knocked down all targets in the Dharmacon™ Lincode™ siRNA Library collection (currently 2,231) in both cell lines and quantitated changes using high content imaging. Here we report the functional consequences of lncRNA knockdown in breast cell lines and correlate with patient tumor data.
Inhibition of The Auto-inflammation Suppressor Protein ISG15 Triggers Preeclampsia by Blocking Trophoblast Migration and InvasionPoster
In summary, ISG15 expression levels are crucial for trophoblast morphology and function (migration/invasion). By blocking trophoblast invasion, reduced ISG15 levels could contribute to impaired spiral artery transformation that reduces utero-placental blood flow in preeclampsia. Thus, agents inducing ISG15 expression are likely to be therapeutic in preeclampsia.
An Emerging Phenotype of Partial RAG 1/2 Deficiency Among Young Children with Autoimmunity and Viral InfectionsPoster
We describe the natural history of a cohort of 12 patients with confirmed partial RAG1/2 mutations and autoimmunity at a young age. We were seeking the link between viral infections and autoimmunity and tested candidate biomarkers that may reflect the underlying RAG1/2 protein deficiency.READ MORE
Severe Combined Immunodeficiency (SCID) caused by thymic aplasia due to a mutation in TBX1Poster
We report one of the first cases of TBX1 haploinsufficiency causing complete thymic aplasia and SCID.READ MORE