Alternative splicing is a central mode of gene expression regulation and a major source for generating proteomic and functional diversity in higher eukaryotes. The alternative splicing choice is governed by the splicing enhancer and silencer elements present in the pre-mRNA, which are recognized by RNA binding proteins, such as members of the serine-arginine-rich (SR) protein or hnRNP (heterogeneous nuclear ribonucleoprotein) family and other protein factors. Alternative splicing can be regulated dependent on developmental stage, tissue, disease status, or in response to extracellular stimuli. Mis-regulation of splicing causes a wide range of human diseases including cancers. Accumulating evidence suggested that alternative splicing and splicing regulators are often deregulated in cancers. .Among all cancer types lung cancer represents the most common cause of death worldwid. Non-small cell lung cancer (NSCLC) can be considered as the most frequent subtype of lung cancer. Recently several studies reported the detection of lung cancer-associated alternative splicing changes. However, the mechanisms that regulate alternative splicing during tumorigenesis are not well understood..The overall goal of this proposal is to investigate the functional roles and mechanisms of splicing factors that are deregulated in lung cancer cells. Specific aims are:.1) to identify splicing regulators that are deregulated in lung cancer cells;.2) to characterize functional roles of deregulated splicing regulators in lung cancer cells;.3) to search for target genes of deregulated splicing regulators in lung cancer cells;.4) to study the molecular mechanism used by deregulated splicing regulators to control alternative splicing of target genes..This work should advance our understanding of alternative splicing regulation in lung cancer and hold promise for identifying novel drug targets for therapeutic purposes.