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.
Psychiatric Risk Gene Cacna1c and Early Life Stress: Potential Gene-Environment interactions?Poster
Early life stress (ELS) is highly associated with development of psychopathology
and mood disorders in adulthood. Genetic studies have identified variation in the gene calcium voltage-gated channel subunit alpha1C (CACNA1C) to increase risk for several psychiatric disorders. This poster assessed the expression of Cacna1c following prepubertal stress.
T-helper cell phenotype expression in cutaneous lesions of angioimmunoblastic T-cell lymphomaPoster
Angioimmunoblastic T-cell lymphoma (AITL) is a common type of peripheral T-cell lymphoma. AITL can be missed until lymphadenopathy develops in patients initially presenting with skin lesions, as skin biopsy may lack conclusive findings. Our case highlights the extranodal presentation of AITL with cutaneous lesions displaying the TFH phenotype.READ MORE
Novel Role of the Innate Immune DNA Sensor IFI16 (Interferon Gamma Inducible Protein 16) as a Major Epigenetic Modulator During KSHV Infection and Lytic ReactivationPoster
Studies have shown that IFI16 acts as an antiviral restriction factor against a number of DNA viruses, by inhibiting viral replication or transcription through epigenetic modifications. However, till date, no specific epigenetic function of IFI16 has been identified. Here, we have discovered that IFI16 recruits two histone methyltransferases on the KSHV episome leading to altered Histone H3K9 methylation, thus regulating its lifecycle.READ MORE
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