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Analysis of long non-coding RNA expression and function in a mouse model of glioblastoma

Myskiw, Chad and Kadri, Sabah and Ke, Eugene and Shishkin, Alex and Friedmann-Morvinski, Dinorah and Soda, Yasushi and Guttman, Mitchell and Verma, Inder (2014) Analysis of long non-coding RNA expression and function in a mouse model of glioblastoma. Cancer Research, 74 (19 Suppleme). Art. No. 524. ISSN 0008-5472. http://resolver.caltech.edu/CaltechAUTHORS:20150604-151125153

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Abstract

Glioblastoma (GBM) is the most common adult brain tumor and represents one of the most treatment refractory cancers. Although significant progress has been made in understanding the coding genomic alterations associated with GBM, patient survival rarely exceeds 12-14 months following diagnosis. Long non-coding RNAs (lncRNAs) are RNA species generally classified as > 200 base-pairs in length that lack protein coding potential and therefore exert their function as RNA. Several lncRNAs have been shown to play important roles in cancer biology. Despite this, the role of lncRNAs in cancer, and GBM in particular, remains relatively uncharacterized. We hypothesize that lncRNAs are differentially expressed in GBM and contribute to the pathogenesis of this disease. Using next generation sequencing, we have identified lncRNAs expressed in our mouse model of GBM, initiated by lentivirus-mediated expression of oncogenic Ras and a shRNA targeting p53. This resulted in the identification of 818 putative lncRNAs, the majority of which represent novel, uncharacterized transcripts. The majority of the lncRNAs identified were intergenic and not associated with any known protein coding gene. Of the total lncRNAs, 44% were differentially expressed in tumor tissue compared to normal mouse brain. Expression of a subset of these differentially expressed lncRNAs was validated by real-time PCR. Expression of several of these validated lncRNAs could be altered by direct activation of oncogenic signaling in normal mouse neuroprogenitor cells and astrocytes. Using a combination of computational and molecular biology approaches, we will identify candidate lncRNAs to test in functional assays for their role in glioblastoma biology.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1158/1538-7445.AM2014-524 DOIArticle
http://cancerres.aacrjournals.org/content/74/19_Supplement/524PublisherArticle
ORCID:
AuthorORCID
Guttman, Mitchell0000-0003-4748-9352
Additional Information:©2014 American Association for Cancer Research.
Record Number:CaltechAUTHORS:20150604-151125153
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20150604-151125153
Official Citation:Chad Myskiw, Sabah Kadri, Eugene Ke, Alex Shishkin, Dinorah Friedmann-Morvinski, Yasushi Soda, Mitchell Guttman, Inder Verma. Analysis of long non-coding RNA expression and function in a mouse model of glioblastoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 524. doi:10.1158/1538-7445.AM2014-524
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:58018
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:05 Jun 2015 03:37
Last Modified:27 Oct 2016 18:25

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