ECE2016 Eposter Presentations Obesity (69 abstracts)
A prostate cancer risk associated polymorphism regulates androgen mediated regulation of a novel long noncoding RNA, IRX4lncRNA
Janaththani Panchadsaram 1, , Gregor Tevz 1, , Nataly Stylianou 1, , Brett Hollier 1, , Colleen Nelson 1, , Elizabeth Williams 1, , Judith Clements 1, & Jyotsna Batra 1,
1Australian Prostate Cancer Research Centre – Queensland (APCRC-Q), Translational Research Institute, Brisbane, Australia; 2School of Biomedical Sciences, Institute of Health & Biomedical Innovation, Queensland University of Technology, Brisbane, Australia.
Prostate cancer (PCa) is the second most common cause of cancer death in developed countries. Our RNAseq analysis identified a novel long non-coding RNA, IRX4lncRNA at chromosome 5p15. The expression of IRX4lncRNA was much higher in prostate tumor samples (n=50) compared to their matched controls. Moreover, knockdown of lncRNA reduced the cell proliferation of LNCaP cells and this lncRNA was down-regulated in the cells undergoing Epithelial to Mesenchymal Transition (EMT), which is a hallmark of PCa invasion.
Interestingly, differential regulation of IRX4lncRNA by androgens was observed in VCaP (up-regulated) and LNCaP (down-regulated) cells. In-silico analysis (Cistrome Finder Database) identified binding of two crucial transcription factors- AR and ERG, at this locus in VCaP cells and no AR binding in LNCaP cells (ERG negative). We also noted a correlation between IRX4lncRNA expression and ERG fusion in our RNA-sequencing data of a cohort of seven androgen-responsive patient-derived xenografts. Sequencing of this AR/ERG binding region identified a Multiple Nucleotide Length Polymorphism (MNLP, rs38668493) where a stretch of 47bp sequence is replaced by a novel 21bp sequence. VCaP cells have an intact AR/ERG binding site (47bp/47bp) whereas LNCaP cells have a disrupted AR/ERG binding site (21bp/21bp) which may explain the differential androgen responsiveness of IRX4lncRNA. This MNLP is in linkage disequlibrium (LD) with the previously identified PCa risk associated SNP, rs10866528, suggesting this MNLP may possibly be the functional genetic variant at this locus and guiding the AR/ERG binding to this locus and therefore, directing the androgen-mediated regulation of IRX4lncRNA. We are currently focusing on establishing the functional role of this MNLP in PCa.
Volume 41
Article tools
My recent searches
My recently viewed abstracts
Authors
Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
© Bioscientifica 2024 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more