ZIA BC 011397 (ZIA) | |||
---|---|---|---|
Title | Alternative splicing in Ras transformed cells | ||
Institution | NCI, Bethesda, MD | ||
Principal Investigator | Luo, Ji | NCI Program Director | N/A |
Cancer Activity | N/A | Division | CCR |
Funded Amount | $130,717 | Project Dates | 10/01/2010 - N/A |
Fiscal Year | 2011 | Project Type | Intramural |
Research Topics w/ Percent Relevance | Cancer Types w/ Percent Relevance | ||
Cancer (100.0%) Digestive Diseases (60.0%) |
Colon/Rectum (40.0%) Lung (40.0%) Pancreas (20.0%) |
||
Research Type | |||
Normal Functioning Cancer Initiation: Oncogenes and Tumor Suppressor Genes |
|||
Abstract | |||
BACKGROUND Through a RNAi synthetic lethal screen we have identified a number of key mRNA splicing factors to be required for the viability of Ras mutant cancer cells. PURPOSE In this project we aim to address the following questions: 1. the mechanism by which a subset of mRNA splicing factors is synthetically lethal with Ras mutation; 2. which cellular proteins are differentially spliced in Ras mutant cells; 3. How the changes in mRNA splicing pattern in these cells affect their function in the context of Ras mutation SIGNIFICANT MATERIALS AND METHODS 1. shRNAs that target a selected number of splicing factors. 3. RNA-seq protocol for quantifying mRNA splicing pattern changes FY2011 ACCOMPLISHMENT We have validated shRNAs that target a number mRNA splicing factors that are identified to be synthetically lethal with KRAS. We have generated cell lines stably expressing rescue cDNAs to these factors. We are carrying RNA-seq experiments to characterize mRNA splicing patters in KRAS WT and mutant cells and with or without splicing factor knockdown. |